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THE    NATURAL    HISTORY    OF    CANCER 


THE 

NATURAL    HISTORY 
OF   CANCER 


SPECIAL  REFERENCE  TO  ITS  CAUSATION 
AND  PREVENTION 


W.    ROGER    WILLIAMS 

FELLOW  OF  THE  ROYAL  COLLEGE  OF  SURGEONS 


NEW  YORK 
WILLIAM  WOOD  AND  COMPANY 

MCMVIII 


PRINTED  IN  ENGLAND. 


3-  lK8- 


All  rights  reserved 


PREFACE 


THE  subject  of  cancer  has  hitherto  been  investigated  far  too  exclusively 
by  the  pursuit  of  details  in  ultimate  analysis  ;  and  hardly  at  all  by  the 
synthetical  and  comparative  methods,  which  have  been  so  profitably 
employed  in  other  branches  of  biological  research. 

As  that  fine  pathologist  Billroth  has  remarked  :  "  Everything  is  too 
hurried  nowadays.  We  suffer  from  an  insatiable  craving  for  new — or 
apparently  new — facts,  in  the  hope  of  obtaining  a  possible  sensational 
success.  No  time  is  allowed  to  reflect  upon,  or  to  reconsider,  the  onward 
course  of  scientific  inquiry.  Where  are  we  ?  What  have  we  left  behind  ? 
What  is  ahead  ?  Is  it  worth  while  to  go  farther  in  this  direction  or  in 
that  ?  Has  detailed  work  given  us  a  profitable  knowledge  of,  or  an 
insight  into,  the  whole  subject  ?  No  one  finds  time  to  answer  such 
questions." 

In  order  that  the  immense  stores  of  miscellaneous  items  of  knowledge 
accumulated  during  the  last  half-century  by  dispersive  analysis,  may  be 
profitably  utilized  for  cancer  research,  concentration  is  above  all  things 
necessary  ;  for  only  thus  can  a  higher  plane  of  progress  be  attained. 

Moreover,  since  the  cure  of  cancer  altogether  transcends  present 
experience,  I  have  in  this  work  specially  endeavoured  to  elucidate  the 
causation  and  prevention  of  the  disease  rather  than  its  cure  ;  for  which, 
in  my  opinion,  reliable  indications  are  lacking. 

To  this  end  I  have  devised  and  applied  a  new  method  of  cancer 
research — which  may  be  called  synthetic — whereby  I  have  shown  that 
there  are  modes  of  life,  various  habits  and  so  forth,  which  tend  to  prevent 
the  incidence  of  cancer  almost  entirely  in  healthy  stocks,  and  greatly  to 
reduce  its  ravages,  even  among  those  hereditarily  predisposed. 

Such  are  the  objects  to  which  the  present  work  is  dedicated. 

W.  ROGER  WILLIAMS. 

CLIFTON,  BRISTOL, 

April,  1908. 


ERRATUM 

Page  446,  eleventh  line  from  the  top  : 

"  as  well  as  in  the  veins  of  the  lungs,  brain,"  for  "  veins ' 
read  "  bloodvessels." 


CONTENTS 


CHAPTER  I 

INTRODUCTION  , 

PAGES 

The  status  of  pathology  in  the  scientific  hierarchy — The  meaning  of  the  term 
"  natural  history,"  as  here  employed — The  term  "  tumour,"  and  its  signifi- 
cance— Some  generalities  de  tumoribus — "  Malignancy,"  and  what  is  meant 
thereby  :  a  term  that  covers  a  multitude  of  effects — Nothing  specific  about 
malignancy  :  its  physiological  prototypes — The  terms  "  cancer,"  "  epithelioma  " 
(vd  carcinoma),  and  "  sarcoma  "  defined  ...  .  1-11 


CHAPTER  II 
GEOGRAPHICAL  DISTRIBUTION  AND  INCIDENCE 

Preliminary  aperqu — Some  generalities  as  to  the  distribution  of  cancer  among 
mankind — The  influence  of  race,  complexion,  and  conditions  of  existence,  as 
exemplified  by  such  well-marked  racial  types  as  Negroes,  North  American 
Indians,  and  Jews— General  survey  of  the  distribution  of  cancer  in  Europe, 
Asia,  Australia,  Africa,  and  America  -  -  -  12-49 


CHAPTER  III 
THE  INCREASE  OF  CANCER,  AND  ITS  CONCOMITANTS 

The  rise  of  new  diseases  and  the  decline  of  old  ones — The  antiquity  of  cancer — 
Its  increase  in  England  and  Wales  during  the  nineteenth  century,  as  shown 
by  the  Registrar-General's  data,  by  life-insurance  reports,  and  by  other 
evidence — The  reality  of  this  increase — It  has  involved  all  parts  of  the  body, 
without  any  marked  alteration  of  the  old  localization  ratios — The  dispropor- 
tionate increase  among  men — The  concomitant  decline  of  tubercle — JCtio- 
logical  considerations  :  the  relation  to  sudden  environmental  changes  (e.g.,  to 
urbanization  and  prosperity  in  our  country,  to  domestication  and  alimentation) 
— The  doctrine  of  cancer  being  morbus  miseries  is  refuted — The  undue  preva- 
lence of  the  disease  among  the  well-to-do  and  easy-going — The  increase  and 
its  concomitants  in  Scotland,  Ireland,  Switzerland,  Denmark,  France,  Sweden, 
Holland,  Germany,  Austria,  Italy,  United  States,  Australia,  and  New 
Zealand  --------.  50-78 


CHAPTER  IV 
£THE  TOPOGRAPHICAL  DISTRIBUTION  OF  CANCER 

The  researches  of  Moore  and  Haviland — The  persistence  of  the  topographical 
variations  in  the  incidence  of  cancer  in  the  chief  divisions  of  England  and 
Wales  during  the  last  half-century — These  variations  are  shown  to  be  inde- 
pendent of  the  diversities  in  the  age  and  sex  distribution  of  the  population — 
Reasons  for  believing  that  they  are  mainly  the  outcome  of  divergent  conditions 
of  existence  ...-....' 


x  CONTENTS 

CHAPTER  V 
CANCER  AND  OTHER  TUMOURS  IN  ANIMALS 

PAGES 

The  comparative  pathology  of  tumours  still  in  a  backward  condition— The  similarity 
between  human  and  animal  tumours  :  morphological  and  setiological— The 
influence  of  sex  and  age — The  much  greater  proclivity  of  domesticated  than 
of  wild  animals  to  tumours— The  special  frequency  of  malignant  tumours  in 
castrated  animals  of  both  sexes,  and  its  significance — The  rarity  of  malignant 
and  other  tumours  in  monkeys  :  their  proclivity  to  tubercle— Malignant  and 
other  tumours  in  dogs,  cats,  horses,  mules,  asses,  oxen,  pigs,  sheep,  goats, 
deer,  rabbits,  mice,  rats,  and  other  mammalian  animals  ;  in  birds,  reptiles, 
amphibia,  and  fishes — The  comparative  pathology  of  the  invertebrata  is  prac- 
tically terra  incognita— The  frequency  of  quasi -malignant  pseudo-plasms  in 
animals— Tubercle  in  the  animal  world  .....  87-114 


CHAPTER  VI 
TUMOURS  IN  VEGETABLE  ORGANISMS 

Tumours  analogous  to  those  of  human  and  animal  pathology,  occur  also  in  the 
vegetable  world  —  Their  relation  "to  bud  formation  —  Adventitious  buds  and 
bud  variation — Local  hypertrophies — Circumscribed  non-malignant  tumours 
(Knaurs  etc.) — Woody  outgrowths  and  excrescences — "  Broussins  "  constitute 
the  nearest  approach  in  vegetable  pathology  to  the  malignant  tumours  of 
human  and  animal  pathology — Their  special  features  :  illustrative  cases — The 
great  frequency  of  highly-evolved  pseudo-plasms  in  vegetable  organisms  :  galls 
and  other  tumour-like  new  formations  :  their  pathogenesis,  development,  and 
life-history  -  -  115-128 


CHAPTER  VII 
THE  GENESIS  OF  MALIGNANT  TUMOURS 

Historical  review.  The  author's  modified  cell  theory  of  tumours— The  present 
controversy— Are  tumours  essentially  of  intrinsic  or  extrinsic  origin  ?— The 
general  theory  of  intrinsic  pathogenesis— Tumour  formation  as  a  special  form 
of  overgrowth  of  the  individual :  gemmation— Variation,  mutation,  and  tumour 
formation— Developmental  irregularity,  with  special  reference  to  the  role  of 

rests  "  in  the  origin  of  tumours— The  classification  of  tumours  as  (1)  teratoid 
(blastogenicj.and  (2)  histioid  (somatogenic)— The  genesis  of  teratoid  tumours 

-1  he  genesis  of  histioid  tumours :  congenital  defects  and  tumour  formation— 
Histioid  tumours  and  pre-natal  developmental  irregularities,  as  illustrated  by 
the  genesis  of  uterine  and  mammary  tumours  -  -  .  129-168 


CHAPTER  VIII 
THE  EXPERIMENTAL  STUDY  OF  CANCER  GENESIS 

Grafting  experiments  with  normal  tissues  of  pre-  and  post-natal  origin— Regenera- 
tive  and  hyperplastic  processes,  and  their  resemblance  to  cancerous  processes- 
Deductions  therefrom-Grafting  experiments  with  epidermoidal  and  connective- 
t  ssue  structures— Grafting  entire  organs  or  large  parts  of  the  same— Implanta 
tion  experiments  with  papillomatous  and  other  non-malignantlumour?  with 
special  reference  to  human  condylomata  and  to  the  contagious  venereal  tumours 
aoga— ine  many  noxious  agents  capable  of  exciting  proliferative  activitv  in 

E™  m     t°W'  T  irrrante  °*  eXtm  may  6XCite  Ce'tain  f^ative  reactions 
Experiments  with  malignant  tumours-Jensen's  mouse  tumour.     Grafting 

2H*S'?iJ?*5?1  ani-mas    of-the  sam«  ^d  different   species-Thf 


an 

question  as  to  the  transmissibility  of  cancer  between     umatem-Auto 
implantation  of  malignant  tumours  in  man  and  animals     -  169-200 


CONTENTS  xi 

CHAPTER  IX 

CANCER  AND  TUMOUR  GROWTH  IN  RELATION  TO  GROWTH  IN 
GENERAL 

PAGES 

The  distinction  between  genesis  and  growth — The  growth  of  ova  and  tumour  germs 
— Of  growth  in  unicellular  and  multicellular  organisms — The  rhythm  of  growth 
and  its  relation  to  the  conditions  of  nutrition  in  reproduction  and  tumour  forma- 
tion— Polarity — The  essential  constituents  of  a  typical  cell— The  integration  of 
multicellular  organisms — The  causative  factors  of  growth — Parthenogenesis, 
metagenesis,  and  alternation  of  generations  in  relation  to  nutrition — Fertiliza- 
tion and  its  artificial  production  :  the  experiments  of  Mead,  Hertwig,  Morgan, 
and  Loeb — The  nucleus  :  its  chromatin  and  chromosomes — Reduction  of  the 
chromosomes  and  its  significance — Tumours  as  disturbances  of  the  rhythm  of 
growth,  owing  to  altered  conditions  of  nutrition — Tumour  growth,  like  discon- 
tinuous growth  in  general,  is  a  disintegrative  process — The  antagonism  between 
the  forces  of  growth,  development,  reproduction,  and  tumour  formation — 
Neoplasia  as  a  lapse  from  predominant  gamogenesis  in  the  direction  of  agamo- 
genesis — The  reproductive  properties  of  somatic  and  germ  cells  are  the  same 
in  kind,  and  differ  only  in  degree  —  The  qualities  of  malignant  and  non- 
malignant  tumours  explained  from  this  standpoint — Nutrition  and  tumour 
growth — Cancer  in  relation  to  decline  of  reproductive  power  ;  its  special 
frequency  after  removal  of  the  sexual  glands  or  their  destruction  by  disease — 
Metabolism,  internal  secretions,  and  cancer — The  influence  of  traumata, 
microbes,  various  chemical,  electrical,  thermal,  mechanical,  and  other  extrinsic 
stimuli — The  cytological  mechanics  of  tumour  growth,  with  special  reference 
to  the  questions  of  self-fertilization,  reduction  of  chromosomes,  the  role  of  the 
centrosome  etc. — Chemical  researches  :  the  question  of  specific  enzymes  etc. — 
The  failure  to  demonstrate  a  specific  causative  factor  for  cancer,  and  its  signifi- 
cance— Growth,  repair,  regeneration,  and  tumour  formation  -  -  201-228 

CHAPTER  X 
THE  MICROBIC  THEORY  OF  CANCER 

Some  general  considerations — Do  all  the  biological  characters  of  tumours  testify 
against  their  parasitic  origin  ? — The  inconclusiveness  of  the  evidence  hitherto 
adduced  as  to  the  existence  of  specific  cancer  microbes — The  search  for  a 
definite  materies  morbi.  The  "  parasitology  "  of  cancer. — Bacterial  "cancer 
parasites  ":  the  claims  of  Rappin,  Schill,  Francke,  Schuerlen,  Freire,  Lampiazi- 
Rubino,  Sanarelli,  Kiibasoff,  Moty,  Maragliano,  and  Doyen — General  conclu- 
sions as  to  bacteria.  Protozoan  "  cancer  parasites  ":  the  claims  of  Hake, 
Pfeiffer,  Thoma,  Darier,  Malassez,  Albarran,  Wickham,  Metchnikoff,  Soudake- 
wich,  Ruffer,  Foa,  Cattle,  Adamkiewicz,  Jackson  Clarke,  D'Arcy  Power,  Kur- 
loff,  Bosc,  Plimmer,  Leyden,  Sjobring,  Schiiller,  Olt,  Bruaudet,  Gaylord, 
Feinberg,  O.  Schmidt,  Podvyssotski,  Robertson,  and  Wade — General  conclu- 
sions as  to  protozoa.  Blastomycetic  and  mould-like  "  cancer  parasites  ":  the 
claims  of  Russell,  Sanfelice,  Roncali,  Maffuci  and  Sirleo,  Corselli  and  Frisco, 
Busse,  Kahane,  Curtis,  Monsarrat,  Leopold,  Wlaeff,  Skchiwan,  Bra,  Niessen 
and  Braithwaite— Blastomycetic  dermatitis — De  Backer's  tentatives — General 
conclusions  as  to  blastomycetes  etc.  The  question  of  infection  :  "  cancer 
epidemics,"  "  cancer  districts,"  "  cancer  houses  "  etc.  -  -  229-269 

CHAPTER  XI 
INFLAMMATION,  TRAUMA,  AND  OTHER  EXTRINSIC  FACTORS 

The  antithesis  of  the  processes  involved  in  inflammation  and  tumour  growth,  with 
demonstration  of  the  fundamental  misconception  underlying  the  ancient  belief 
as  to  their  identity — What  is  "  chronic  inflammation  "  ? — The  Broussaisian  doc- 
trine— Is  cancer  the  outcome  of  inflammation  ? — Pre-cancerous  conditions — 
Antecedent  inflammatory  affections,  and  cancer  of  the  female  breast — Child- 
bearing,  lacerations,  "  endometritis  "  etc.,  in  relation  to  uterine  cancer — The 
rarity  of  cancer  of  the  procident  uterus — Gastric  ulcer  and  gastric  cancer — 
Gall-stones  and  cancer  of  the  gall-bladder — Phimosis  and  cancer  of  the  penis — 
"  Paget's  disease,"  and  cancer  of  the  breast  —  Leucoplasia,  syphilis,  and 
smoking,  in  relation  to  lingual  and  buccal  cancer — Traumata  and  cancer — 
"  Traumatic  malignancy  "  -  -  ....  270-288 


xii  CONTENTS 


CHAPTER  XII 

THE  QUESTION  OF  THE  ORIGIN  OF  MALIGNANT  FROM  NON-MALIGNANT 
TUMOURS 

PAGES 

The  important  practical  issues  involved  in  this  question— The  ancient  belief  in  the 
liability  of  non-malignant  tumour-like  swellings  to  become  malignant,  shaken 
by  the  utilization  of  the  microscope  for  diagnostic  purposes — Modern  research 
shows  that  non-malignant  tumours  have  no  special  proclivity  to  malignancy — 
Discussion  of  the  evidence  in  detail  for  some  notable  examples  (e.g.,  uterine 
myoma,  mammary  nbro-adenoma,  and  ovarian  cystoma) — All  kinds  of  benign 
tumours  may  exceptionally  develop  malignancy,  but  it  is  shown  that  none  of 
them  have  any  special  proclivity  that  way  -  -  289-297 


CHAPTER  XIII 

MULTIPLE  PRIMARY  CANCER,  AND  THE  ASSOCIATION  OF  CANCER  WITH 
OTHER  TUMOURS 

Although  the  initial  lesion  of  cancer  is  generally  solitary,  yet,  of  late,  many  examples 
of  primary  multiplicity  have  been  reported — The  like  is  true  of  most  non- 
malignant  tumours,  and  of  the  developmental  anomalies  per  excessum — 
Bilateral  examples  of  primary  multiplicity  by  no  means  very  exceptional  : 
instances  in  the  mamma,  ovary,  testis,  kidney,  adrenal,  retina  etc. — Other 
examples  of  primary  multiplicity  (e.g.,  in  the  skin,  uterus,  mamma,  gastro- 
intestinal tract  etc.) — General  conclusions  as  to  primary  multiplicity — The 
question  of  mixed  malignant  tumours  (sarco-epithelioma) — The  association  of 
malignant  with  non-malignant  tumours  -  -  298-311 


CHAPTER  XIV 
THE  INFLUENCE  OF  SEX 

The  localization  and  incidence  of  tumours  (malignant  and  non-malignant)  is  much 
influenced  by  sex — Author's  analysis  of  15,481  consecutive  cases — Diversities 
in  sex  incidence  are  due  to  biological  peculiarities  of  the  affected  parts,  rather 
than  to  any  general  constitutional  condition  correlated  with  sex — Evidence 
from  the  national  mortality  returns  as  to  the  sex  incidence  of  cancer — Qualifying 
considerations— Sex  in  relation  to  localization  and  age  incidence  -  -  312-316 


CHAPTER  XV 
THE  INFLUENCE  OF  AGE 

The  importance  of  age  incidence  in  the  aetiology  of  cancer — The  facts  as  to  the 
age  distribution  of  cancer,  as  revealed  by  the  national  mortality  reports,  and 
by  hospital  statistics — To  appreciate  the  significance  of  those  facts,  some 
knowledge  as  to  the  role  of  age  in  relation  to  mortality  in  general  is  needed— 
Thus  regarded,  the  characteristic  feature  of  the  age  incidence  of  cancer  is  shown 
to  be,  not  its  progressive  increase  with  advancing  years  (for  this  it  shares 
with  other  lethal  maladies),  but  its  disproportionate  augmentation  in  post- 
meridian life— Centenarians  and  other  very  aged  persons  are  shown  to  be  but 
little  prone  to  malignant  tumours— Cancer  is  not  a  senile  disease— The  special 
feature  of  the  age  incidence  of  cancer  is  its  connexion  with  the  decline  in 
reproductive  activity— Age  and  sex  incidence  in  respect  to  localization— Early- 
life  malignant  tumours  are  sarcomata  :  pre-natal  cases— The  localization  of 
these  early-hfe  malignant  tumours  is  very  different  from  that  of  similar  tumours 
met  with  in  later  life.  Malignant  epithelial  tumours  are  almost  unknown  prior 
to  puberty  and  of  great  rarity  under  the  age  of  twenty  :  examples  of  early- 
life  epithehoma  in  such  representative  sites  as  the  rectum,  stomach,  uterus, 
and  mamma— Resume  of  the  facts  and  general  conclusions  -  -  317-331 


CONTENTS 


CHAPTER  XVI 

/ETIOLOGICAL  INDICATIONS  DERIVED  FROM  THE  STUDY  OF  THE  LIFE-HISTORY 
OF  CANCER  PATIENTS 

PAGES 

Nutrition  and  cancer — The  cancer  type  of  organization — Obesity — Blood-pressure 
— Diabetes — Arthritism  and  cancer — Osteitis  deformans— Gall-stones — The 
inter-relations  of  tubercle  and  cancer— Pleural  adhesions,  emphysema,  cardiac 
changes  etc.— Malaria — Syphilis  and  cancer — Erysipelas,  suppurative  affec- 
tions, and  infectious  diseases — Insanity  and  cancer — Grief,  anxiety,  and 
mental  distress — The  rarity  of  cancer  in  prison  inmates,  paupers,  convents  etc. 
— Dermatoses  in  the  cancerous — Paralysed  parts  and  cancer — Menstruation — 
Alimentation— Salt  and  cancer— Alcohol— Water— Late  marriages,  decline  in 
fertility,  celibacy  etc.  —  Occupation  and  social  status  as  influencing  the 
proclivity  to  cancer  -  332-355 


CHAPTER   XVII 
FAMILY  HISTORY 

Physiological  heredity,  pathological  heredity  and  the  vis  medicatrix  natures — 
Darwinism  and  Weismannism — The  evidence  from  the  study  of  disease, 
especially  malignant  and  non-malignant  tumours — Multiple  family  cancer  : 
remarkable  examples  in  mammary,  uterine,  gastric,  intestinal,  ocular,  and 
other  local  forms  of  cancer — Cancer  in  twins — Glioma — Instances  of  the 
inheritance  of  non-malignant  tumours — The  predominance  of  homotopic 
transmission — Family  history  analyses — Direct,  indirect,  and  atavistic  trans- 
mission of  cancer — Single  family  prevalence — Consanguinity — Hereditary  pro- 
clivities correlated  with  cancer,  viz.,  tubercle,  insanity,  apoplexy,  arthritism, 
longevity,  and  excessive  fecundity  -  -  356-374 


CHAPTER  XVIII 

THE  INITIAL  SEATS  OF  TUMOURS,  AND  THEIR  RELATIVE  FREQUENCY 

Like  normal  parts  of  the  body,  tumours  have  their  own  individuality  ;  hence,  in 
studying  their  life-history,  pre-existing  structural  peculiarities  cannot  be 
ignored — Neoplastic  areas  are  rich  in  cells  still  capable  of  growth  and  pro- 
liferation— Analyses  showing  the  site  incidence  of  tumours,  based  on  15,481 
hospital  cases — Tumours  seldom  originate  from  obsolete  and  highly  specialized 
structures — The  initial  seats  of  malignant  epithelial  tumours,  in  both  sexes,  as 
determined  by  hospital  statistics  and  the  national  mortality  returns — The  pro- 
clivity of  tumours  for  certain  regions  of  particular  organs,  as  illustrated  by  the 
uterus,  mamma,  stomach,  intestine,  skin  etc. — The  question  of  trophic  nerve 
influence  in  localization — The  site  incidence  of  sarcoma  and  of  non-malignant 
tumours  and  cysts — Analytical  tables  showing  the  initial  seats  of  malignant 
and  non-malignant  tumours,  and  their  relative  frequency  -  -  375- 


CHAPTER  XIX 
THE  MORPHOLOGY  OF  MALIGNANT  TUMOURS 

The  primary  tumour  and  its  growth — The  physiological  characters  of  cancer  cells  : 
their  growth  and  proliferation — Nuclear  changes  :  the  heterotypical  mitosis — 
"  Ponts  intercellulaires  " — There  is  nothing  specific  about  cancer  cells  and 
cancer  structures — The  stroma,  lymphatics,  bloodvessels,  and  nerves — Chemical 
analysis — Enzymes  :  the  question  of  a  special  cancer  ferment  etc. — Pre- 
cancerous  changes  —  Local  dissemination  —  Lymphatic  "  permeation  "- 
Lymph-gland  dissemination  vi&  the  thoracic  duct — The  left  supra-clavicular 
adenopathy  (Troisier's  symptom),  and  its  significance — General  dissemination 
— The  question  of  dissemination  by  non-malignant  tumours  etc. — The  similarity 
between  the  primary  tumour  and  its  secondaries — The  metastases  of  malignant 
epithelial  and  connective-tissue  tumours  contrasted — General  conclusions  as  to 
metastasis — The  theory  of  metastasis — The  varieties  of  malignant  tumours  400-453 


xiv  CONTENTS 

CHAPTER   XX 
RECURRENCE 

PAGES 

Local,  lymph-glandular,  and  raetastatic  recurrence— Epitheliomatous  and  sarcoma- 
tous  tumours  contrasted  in  respect  to  their  recurrences — Some  typical  examples 
—The  period  at  which  recurrence  supervenes  :  its  variability  ;  early  and  late 
recurrences— The  "  recurrence  "  of  ovarian  cystoma— The  frequency  of  malig- 
nant and  non-malignant  recurrence  after  ovariotomy  for  cystoma— The  influ- 
ence of  diseased,  absent,  and  defective  ovaries  on  recurrence — The  effect  of 
castration — The  rationale  of  malignant  recurrence  -  -  454-467 


CHAPTER  XXI 

CACHEXIA 

Cachexia  may  be  associated  with  other  morbid  conditions  besides  cancer  ;  there  is, 
therefore,  nothing  specific  about  it — The  cachexia  of  cancer  a  consequence  of 
the  primary  tumour — It  is  probably  due  to  toxic  albuminoids  in  the  circula- 
tion, derived  from  the  disintegrating  cancer  cells — The  blood  changes — The 
significance  of  leucocytosis— The  agglutin  reaction— No  specific  opsonin— The 
clinical  symptoms  of  cachexia— Peripheral  neuritis  etc.— Fatty  degeneration 
— Osteomalacia — The  condition  of  the  urine — The  rarity  of  amyloid  degenera- 
tion and  of  fever— Death  by  asthenia  -  -  468-478 


CHAPTER  XXII 
QUASI-MALIGNANT  PSEUDO-PLASMS 

The  difficulties  in  the  diagnosis  of  cancer,  and  their  causes — Chronic  inflammatory, 
tuberculous,  and  syphilitic  quasi-malignant  lesions — Mycotic,  microbic,  and 
other  parasitic  pseudo-plasms  resembling  cancer — Examples  in  mammary  and 
cutaneous  locations — The  so-called  "  withering  sarcomata,"  and  the  question 
of  cancer  cures — The  frequency  of  similar  pseudo-plasms  in  animals  -  479-486 


CHAPTER  XXIII 

INFLAMMATION,  ULCERATION,  RETROGRESSION,  AND  SPONTANEOUS 
CURE 

The  comparative  rarity  of  suppuration  of  malignant  tumours — The  question  of  cure 
by  ulceiation,  sloughing,  and  gangrene — Casoating  cancers — Retardation, 
arrest,  and  retrogression — Illustrative  cases — The  conditions  under  which  such 
changes  occur — The  starvation  treatment  of  cancer — The  question  of  spon- 
taneous cure  ........  487-496 


INDEX  OF  SUBJECTS       ...  .     497-507 

INDEX  OF  NAMES  OF  AUTHORS  CITED  -  ...  .     508-519 


THE  NATURAL  HISTORY  OF  CANCER 


CHAPTER  I 
INTRODUCTORY 

The  Status  of  Pathology,  and  the  Meaning  of  the  Term  "  Natural 
History"  as  here  Employed. 

IT  may  be  said  of  each  particular  science — as  of  science  in  general — that 
it  has  been  gradually  evolved.  But  this  process  has  affected  the  various 
sciences  very  unequally,  so  that  while  some  have  nearly  attained  the 
highest  degree  of  perfection,  others  are  still  in  a  crude,  infantile,  or 
undeveloped  state. 

In  accordance  with  these  ideas,  the  sciences  may  be  classified  in  a 
hierarchical  manner,  according  to  their  state  of  perfection  and  degree  of 
evolution,  with  mathematics  and  astronomy  at  one  end  of  the  series, 
and  the  biological  sciences — which  include  pathology — at  the  other. 

In  the  intellectual  progress  of  the  nineteenth  century,  the  chief  event 
has  been  the  translation  of  these  immature  biological  sciences  from  the 
domain  of  empiricism,  to  their  proper  place  in  the  scientific  hierarchy. 

So  far  as  pathology  is  concerned,  however,  this  great  movement  is 
still  in  its  infancy  ;  for  although  the  medical  art  has  been  practised  from 
time  immemorial,  it  is  only  since  the  beginning  of  the  nineteenth  century 
that  the  crude  data  thus  laboriously  acquired,  have  begun  to  be  treated 
scientifically.  There  has  been  no  Comte,  Spencer,  or  Darwjn  to  lighten 
the  darkness  of  modern  pathology.  \J&*j~  oJn>v$  1/ti  chnJ  '. 

It  is  necessary  at  the  outset  to  refer  thus  pointedly  to  the  crudeness 
and  immaturity  of  medical  knowledge,  because  nowhere  do  these  qualities 
find  more  striking  exemplification,  than  in  the  terrible  welter  of  disjointed 
facts  and  contradictory  hypotheses,  that  constitute  such  a  large  part  of 
modern  "  tumour  science." 

Owing  to  the  progress  of  knowledge,  successive  generations  view  the 
problems  presented  by  the  phenomena  of  disease  from  different  stand- 
points— hence  every  age  needs  its  own  interpreters.  This  is  specially 
true  of  the  vast  subject  of  onkology.  It  will  be  my  endeavour  in  what 
follows  to  reduce  into  some  semblance  of  order  these  vast  masses  of 
chaotic  materials,  and  to  deduce  from  them  such  conclusions  as  the  facts 
seem  to  warrant.  In  doing  this  I  shall  not  scruple  to  avail  myself  of 
hypotheses,  when  these  seem  likely  to  aid  the  investigation  ;  for,  as  Comte 

1 


2  THE  NATURAL  HISTORY  OF  CANCER 

says  :  "  Si  en  contemplant  les  phenomenes,  nous  ne  les  rattachions  point 
immediatement  a  quelques  principles,  non-seulment  il  nous  serait 
impossible  de  combiner  ces  observations  isolees,  et  par  consequent  d'en 
tirer  aucun  fruit,  mais  nous  serions  meme  entierement  incapables  de  les 
retenir  ;  et  le  plus  sou  vent  les  faits  resteraient  inapergus  sous  nos  yeux." 
The  history  of  every  branch  of  medical  knowledge  teems  with  illustrations 
of  the  truth  of  this  luminous  statement. 

By  all  means  let  pathologists  observe  and  experiment,  but  let  them 
not  neglect  to  compare,  systematize,  filiate,  and  reason  on  the  knowledge 
thus  acquired — in  a  disinterested  way — as  if  they  were  dealing  with  a 
problem  of  natural  history ;  and,  above  all,  it  must  never  be  forgotten 

V/.that  comparison  is  the  great  organon  of  biological,  and  consequently  also 
of  pathological,  research. 

Hitherto  research  has  been  far  too  exclusively  directed  to  the  histo- 
logical,  morphological,  and  experimental  conditions  of  tumours,  while 

^the  ensemble  of  their  characters  and  their  inter-relations  with  other 
biological  processes  have  been  but  little  studied.  The  object  of  the 
present  work  is  to  remedy  these  defects  by  giving  a  right  bent  to  research, 
and  a  scientific  basis  to  the  pathology  of  cancer  and  tumour  formation. 
To  effect  this  we  must  work  on  a  broader  basis  than  has  hitherto  been 

'  customary.  As  Bacon1  has  insisted,  in  dealing  with  matters  of  this 
kind  :  "  The  first  object  must  be  to  prepare  a  history  of  the  phenomena 
to  be  explained,  in  all  their  modifications  and  varieties.  This  history 
should  comprehend  not  only  all  such  facts  as  spontaneously  offer  them- 
selves, but  all  the  experiments  instituted  for  the  sake  of  discovery  or  for 
any  other  purposes.  It  ought  to  be  composed  with  great  care  ;  the  facts 
accurately  related  and  distinctly  arranged  ;  their  authenticity  diligently 
examined  ;  those  that  rest  on  doubtful  evidence,  though  not  rejected,  yet 
noted  as  uncertain,  with  the  grounds  of  the  judgment  so  formed.  This 
last  is  very  necessary,  for  facts  often  appear  incredible  only  because  we 
are  ill-informed.  This  record  of  facts  is  Natural  History." 

Such  is  the  method  I  propose  to  employ  in  the  present  undertaking. 

The  Term  "  Tumour." 

It  is  in  consequence  of  such  conditions  as  those  above  mentioned,  that 
so  many  of  the  leading  pathological  terms  are  without  precise  significance. 
Thus  the  word  "  tumour,"  by  which  we  connote  the  various  pathological 
formations  with  which  this  work  is  concerned,  has  not  only  been  inter- 
preted differently  in  different  ages,  but  also  by  authors  living  in  the  same 
age,  and  this  diversity  is  still  apparent.  A  generally  acceptable  definition 
is,  I  think,  hardly  likely  to  be  arrived  at,  until  we  have  attained  more 
uniformity  in  our  conceptions  as  to  the  origin  and  causation  of  these 
formations. 

By  the  Latins,  who  gave  us  the  term,  any  unusual  kind  of  swelling 

was  called  "  tumor  "  ;  thus  Galen  and  his  followers  describe  :  "  Tumores 

secundum  naturam  supra  naturam  et  praeter  naturam."     In  the  first 

group  they  included  physiological  enlargements,  in  the  second  swellings 

1  "  Novum  Organum,"  ii. 


INTRODUCTORY  3 

due  to  displacement  of  natural  parts,  while  the  third  embraced  all  other 
swellings — a  miscellaneous  assemblage,  comprising  all  that  has  since  been 
included  under  the  term  "  tumour,"  and  many  other  conditions. 

The  tendency  of  subsequent  ages  has  been  to  restrict  the  use  of  this 
term  to  a  much  narrower  range.  Virchow,  however,  classed  as  tumours 
nearly  all  chronic  inflammatory  and  granulomatous  formations,  which 
are  now  generally  regarded  as  being  altogether  outside  this  category. 

Recently  the  term  "  neoplasm  "  has  obtained  currency  as  a  synonym 
for  "  tumour,"  for  which  the  old  Greek  word  was  6'y/co<?,  whence  this 
study  has  been  designated  "  onkology." 

Many  and  various  are  the  tentatives  that  have  been  made  to  define 
the  term  "  tumour,"  but  it  cannot  be  said  that  any  of  them  are  really 
satisfactory.  No  doubt  John  Hunter  realized  this  when  he  said  :  "  Of 
all  things  on  the  face  of  the  earth  definitions  are  the  most  cursed  "  ;  and 
Virchow  was  nearly  as  emphatic  with  his  famous  dictum  :  "  No  human 
being  can  define,  even  under  torture,  exactly  what  a  tumour  is."  Thus 
we  reach  the  conclusion  that  tumours,  like  other  biological  conceptions, 
do  not  admit  of  strictly  logical  definition. 

For  practical  purposes,  however,  a  tumour  may  be  defined  as  a 
persistent  mass  of  redundant  new  formation,  not  obviously  due  to  any 
extrinsic  cause,  which  grows  independently  of  the  body,  with  which  it  is 
structurally  and  functionally  uncombined  ;  so  that,  although  it  generally 
assumes  a  more  or  less  circumscribed  form,  it  is  nevertheless  distinct 
from  any  known  anomaly. 

From  the  biological  standpoint,  tumour  formation  may  be  regarded  as 
a  phenomenon  of  the  same  order  as  reproduction  in  general — that  is  to 
say,  as  a  special  form  of  overgrowth  of  the  individual.  This  implies 
^recognition  of  the  affinity  between  tumour  formation  and  morphological 
variation  in  general,  which  has  hitherto  been  generally  overlooked, 
much  to  the  detriment  of  progress  in  tumour  science.  It  will  be  main- 
tained in  the  sequel  that,  in  ultimate  analysis,  a  tumour  is  the  outcome  of 
an  abortive  attempt  of  certain  cells  to  repeat  agamically  some  portion 
of  the  normal  ontogeny — hence  individuation  is  the  cardinal  feature  of 
every  tumour.  What  is  variation  but  a  novel  kind  of  cell  multiplication  ? 
And  what  is  tumour  formation  but  a  special  variety  of  this  novelty  ? 
And  is  not  every  variation,  as  suggested  by  Virchow,  essentially  patho- 
logical in  origin  ?  Variation,  mutation,  and  tumour  formation — what  are 
these  but  different  degrees  of  the  same  process,  wrhich,  being  maintained 
continuously  from  the  germ  to  the  latest  period  of  life,  determines  all 
organic  formation  ?  In  the  sequel  it  will  be  shown  that  the  determining 
factor,  the  true  cause  of  all  these  variations,  is  nutrition — using  the 
term  in  its  widest  sense. 

Such  is  the  thesis  I  now  propose  to  maintain. 

Some  Generalities  de  Tumoribus. 

In  investigating  the  structure  and  development  of  tumours,  it  is 
impossible  for  the  observer  to  escape  the  conviction  that  the  phenomena 
met  with  have  their  counterparts  in  the  normal  evolution.  Tumours, 

1—2 


4  THE  NATURAL  HISTORY  OF  CANCER 

like  other  organic  structures,  ultimately  depend  upon  the  processes  of 
growth  and  reproduction  going  on  in  the  cells  of  the  part  whence  they 
originate,  whether  these  are  of  pre-  or  post-natal  origin.  Pathological 
and  physiological  cells  are  alike  in  their  morphological  and  vital  properties. 
Cell  and  nuclear  division  conform  to  the  physiological  type,  even  as  to 
the  details  of  karyokinesis.  In  both  cases  the  tendency  of  the  newly 
formed  cells  to  revert  to  the  parental  type  is  perfectly  obvious,  and  this 
is  specially  manifest  when  the  tumour  cells  become  converted  into  tissues. 
Hence  the  same  tumour  can  only  be  found  again,  in  exactly  the  same 
situation.  Thus  it  happens  that  throughout  the  whole  range  of  tumour 
structures  no  elements  of  new  and  specific  type  can  be  found,  but  we 
everywhere  meet  with  structures  which  resemble  the  physiological  struc- 
tures, both  genetically  and  histologically.  In  short,  tumours  are  never 
of  such  a  monstrous  nature,  as  not  to  present  some  analogy  with  the  corre- 
sponding pre-existing  structures  of  the  part  whence  they  originate,  either 
in  their  embryonic  or  post-embryonic  states.  Hence  no  study  of  the  life- 
history  of  tumours  can  be  complete,  which  ignores  pre-existing  structural 
peculiarities. 

But  behind  these  structural  changes  we  must  remember  there  always 
are  functional  changes,  although  ordinarily  we  hear  very  little  of  them 
in  connexion  -with  modern  studies  on  tumour  genesis.  We  may,  however, 
be  certain  that  tumours,  like  other  morphological  variations,  are  ulti- 
mately the  outcome  of  the  interactions  of  function  and  structure. 

Tumours  grow  and  are  nourished  like  normal  parts  of  the  body,  yet, 
in  return  for  the  nutriment  thus  supplied,  they  contribute  to  it  nothing 
useful ;  indeed,  their  relation  to  the  rest  of  the  organism  differs  but  little 
from  that  of  parasitism. 

Malignancy. 

Even  if  pathology  were  as  highly  perfected  as  botany  and  zoology, 
pathological  classifications  would  never  have  the  same  significance  as 
botanical  and  zoological  taxonomies,  because  of  the  instability  and  muta- 
bility of  pathological  processes  and  products.  Nevertheless,  even  patho- 
logical classifications  are  useful,  if  only  in  that  they  compel  order  in  our 
conceptions. 

Tumours  have  been  classified  on  many  bases — physiological,  morpho- 
logical, chemical,  genetical,  setiological  etc. ;  but  by  far  the  oldest  and 
most  generally  useful  classification  is  that  which  divides  them,  according 
to  their  physiological  properties,  into  the  malignant  and  non-malignant, 
and  for  our  immediate  purpose  this  will  suffice.  Here,  however,  it  must 
be  noted  that  tumours  exhibit  many  degrees  of  malignancy,  both  in  the 
plus  and  minus  directions. 

In  former  times  certain  intractable  diseases  were  commonly  called 
malignant,  under  the  belief  that  they  were  due  to  the  special  influence  of 
malign  or  evil  spirits,  and  it  is  to  this  superstition  that  we  owe  the  term 
as  applied  to  certain  tumours. 

Even  at  the  present  time  it  is  not  easy  to  define  the  precise  signification 
of  this  much-used  term,  which  covers  a  multitude  of  effects,  although,  in 


INTRODUCTORY  5 

a  general  way,  its  meaning  is  intelligible  enough.  Thus,  every  one  under- 
stands that  malignant  tumours  are  intractable,  destructive,  and  tend  to 
a  fatal  end  ;  and  these  results  are  generally  the  direct  consequences  of  their 
malignant  properties. 

These  comprise — (1)  persistence,  with  a  tendency  to  softening  and 
ulceration  ;  (2)  an  infiltrating  mode  of  growth,  so  that  the  margin  of  the 
tumour  interpenetrates  and  destroys  the  surrounding  structures ; 
(3)  dissemination,  by  which  is  meant  the  powrer  of  the  primary  tumour  to 
form  secondary  tumours  like  itself,  (a)  in  the  vicinity  of  the  primary 
tumour,  (6)  in  the  adjacent  lymph  glands  etc.,  and  (c)  in  distant  parts  of 
the  body,  such  as  the  liver,  lungs,  bones  etc.  ;  (4)  recurrence,  or  the 
powder  of  the  tumour  to  grow  again,  even  after  the  most  drastic  attempts 
to  ensure  its  complete  destruction  by  the  knife,  fire,  caustics  etc.  ;  and 
(5)  cachexia,  or  a  certain  impairment  of  the  general  health  with  wasting. 

It  is  in  the  combination  of  these  various  properties,  rather  than  in  any 
one  of  them  taken  by  itself,  that  malignancy  consists,  for,  as  Paget 
remarks  :  "  Each  may  be  absent  in  tumours  having  all  the  other  features 
of  malignancy,  and  certain  of  them  may  be  seen  occasionally  in  tumours 
which,  in  other  respects,  appear  to  be  non-malignant."  Thus  cancer  qua 
cancer,  gives  no  specific  indication  of  its  presence. 

Let  us  consider  this  matter  a  little  more  in  detail. 

First  of  all  with  regard  to  the  item  persistence,  it  can  hardly  be  main- 
tained that  the  essence  of  malignancy  lies  in  it,  for  intractability  is  a 
feature  of  all  tumours,  malignant  and  non-malignant.  Moreover,  many 
tumour-like  swellings  of  granulomatous  nature  may  be  as  intractable  as 
cancer — e.g.,  certain  syphilitic  and  tuberculous  lesions,  mycosis  fungoides, 
mycetoma,  etc. 

A  more  characteristic  feature  of  malignancy  is  infiltration,  which  has 
often  been  regarded  as  distinctive.  Processes  of  the  tumour  substance 
interpenetrate  the  adjacent  structures,  which  they  destroy — as  it  were,  by 
dissolving — and  supplant.  This  mode  of  increase  is  wellnigh  universal 
among  malignant  epithelial  tumours — which  constitute,  according  to  my 
estimate,  85-4  per  cent,  of  all  malignant  tumours — but  among  the  sarco- 
mata it  is  not  so  general. 

In  many  "  chronic  inflammatory  "  processes  infiltration  and  inter- 
penetration  have  been  demonstrated.  Thus,  for  the  uterus,  Friedlander 
and  Councilman  have  shown  that  the  so-called  "  erosions  "  of  the  os 
uteri  are,  in  this  respect,  often  indistinguishable  from  cancer ;  and  we  are 
now  acquainted  with  many  "  chronic  inflammatory  "  lesions  of  the  skin 
and  other  structures,  in  which  the  same  phenomena  have  been  noted. 

In  a  general  way  it  may  be  said  that  this  mode  of  growth  is  one  of 
the  properties,  which  cancer  shares  with  immature  tissues  in  general. 
Thus,  even  in  the  course  of  normal  development — pre-natal  and  post-natal 
— examples  of  it  often  occur,  especially  in  the  evolution  of  glandular  and 
papillated  structures,  in  the  conversion  of  cartilage  into  bone  etc.  But 
perhaps  the  most  apposite  physiological  prototype  of  this  feature  of 
malignancy  is  to  be  found  in  placenta  formation,  when  the  epithelia  of  X>( 
the  trophoblast  and  chorionic  villi  interpenetrate  the  decidual  and 
maternal  tissues  and  destroy  them ;  and,  as  we  now  know,  when  this 


6  THE  NATURAL  HISTORY  OF  CANCER 

process  goes  beyond  certain  limits  a  tumour  results  which  may  be  either 
innocent  or  malignant,  according  to  the  special  circumstances  of  the 
particular  case. 

No  feature  of  malignant  disease  has  been  more  frequently  regarded 
as  pathognomonic  than  "  dissemination "  ;  yet  it  is  asserted  that  non- 
malignant  tumours  occasionally  manifest  this  property,  as  well  as  certain 
pseudo-plasms  of  which  I  shall  have  more  to  say  in  the  sequel. 

It  is  difficult  to  decide  as  to  the  validity  of  the  claim  to  dissemina- 
tion which  has  been  made  for  thyroid  adenomata,  uterine  fibroids,  cer- 
tain ovarian  cystomata  etc.  No  doubt  many  cases  of  this  kind  admit  of 
being  otherwise  explained.  Nevertheless,  recent  investigations  of  the 
changes  taking  place  in  placentation,  "  deportation  of  chorionic  villi." 
"  hydatid  mole,"  and  the  disease  called  "  deciduoma  vel  chorioma" 
seem  to  indicate  that  there  is  nothing  specific  of  malignancy  merely  in 
"  dissemination." 

The  inference  to  be  drawn  from  the  many  instances  of  malignant 
disease  developing  in  the  track  of  operation  wounds,  especially  after  the 
removal  of  non-malignant  ovarian  and  uterine  tumours,  etc.,  to  which  I 
have  specially  called  attention,  is  of  similar  import. 

From  recent  researches  as  to  placentation  it  appears  that,  even  under 
normal  circumstances,  cells  of  the  trophoblast  and  chorionic  villi  con- 
stantly enter  the  maternal  circulation  during  gestation,  where,  as  a  rule 
they  perish  ;  but,  under  circumstances  not  yet  determined,  they  may 
originate  malignant  or  non-malignant  tumours  in  various  more  or  less 
remote  parts  of  the  body,  such  as  the  vagina,  vulva,  or  even  in  the  brain, 
lungs  etc. 

There  are  good  reasons  for  believing  that  the  constituent  cells  of 
most  malignant  tumours  are,  in  like  manner,  constantly  entering  the 
circulation,  where,  as  a  rule,  they  also  perish  and  are  absorbed,  so  that 
only  those  endowed  with  sufficient  vitality  to  overcome  this,  resistance 
originate  dissemination  tumours.  (_f?'v*/fo  / 

To  account  for  these  phenomena,  it  is  assumed  that  the  circulatory 
fluids  contain  some  substance  (antitoxin,  enzyme  etc.)  inimical  to  the 
intruding  cells,  by  virtue  of  which  their  destruction  is  effected  ;  but 
when,  after  a  time,  this  protective  substance  has  become  used  up  or  so 
attenuated  as  to  be  no  longer  effectual,  these  foreign  cells  then  originate 
tumours.  It  certainly  accords  with  this  view,  that  secondary  tumours 
are  seldom  found  during  the  initial  stage  of  malignant  disease. 

It  is  also  noteworthy  that  certain  malignant  neoplasms  rarely  dis- 
seminate— e.g.,  myeloid  sarcoma,  glioma,  and  "  rodent  ulcer  "  ;  moreover, 
even  for  the  same  variety  of  malignant  tumour  in  the  same  locality,  the 
degree  of  dissemination  is  very  variable ;  and  in  all  parts  of  the  body 
dissemination  is  much  influenced  by  the  localization  of  the  primary 
disease.  These  considerations  indicate  that  the  disseniinativeness  of 
malignant  tumours  is,  in  a  measure,  conditioned  by  local  structural  and 
physiological  peculiarities,  which  render  it  easy  for  their  constituent  cells 
to  get  access  to,  to  live  in,  and  to  be  transported  by,  the  adjacent 
lymphatics  and  bloodvessels. 

Recurrence  may  be   regarded  as   a   consequence   of  dissemination, 


INTRODUCTORY  7 

chiefly  of  the  local  kind — that  is  to  say,  as  a  continuation  of  the  disease 
in  surviving  unextirpated  fragments  of  the  primary  tumour  or  its  offsets. 
Indeed,  such  is  the  great  tenacity  of  life  and  the  wonderful  proliferative 
power,  of  even  the  most  diminutive  fragments  of  malignant  tumours  that, 
when  any  of  these  are  left  behind  after  operation,  as  is  usually  the  case, 
they  only  too  frequently  become  fresh  centres  of  disease. 

Just  as  a  Hydra  regenerates  itself  after  mutilation,  and  after  it  has 
been  cut  into  small  pieces,  so  it  is  with  these  malignant  tumours. 

Viewed  in  this  light,  recurrence  is,  of  course,  no  more  specially  dis- 
tinctive of  malignancy  than  dissemination. 

It  accords  with  this,  that  some  of  the  most  inveterate  and  striking 
instances  of  recurrence  are  met  with  among  tumours  not  otherwise 
remarkable  for  their  malignancy,  such  as  rodent  ulcer,  myeloid  and 
spindle-celled  sarcomata,  keloid  etc. 

Moreover,  non-malignant  tumours  sometimes  grow  again  after 
removal,  of  which  examples  are  furnished  by  uterine  myoma,  ovarian 
cystoma.  mammary  fibre-adenoma,  subungual  exostosis,  condyloma, 
warts  etc. ;  and  in  macrodactyly,  even  after  amputation  of  the  affected 
part  with  the  phalanges,  the  giant  growth  has  been  known  to  recur  in 
the  previously  healthy  stump  ;  while  the  recurrence,  after  extirpation,  of 
a  redundant  mammary  structure  has  lately  been  reported. 

The  impairment  of  the  general  health — cachexia — that  is  so  often 
associated  with  malignant  tumours,  never  precedes  the  outbreak  of  the 
primary  disease — hence  we  infer  that  it  is  a  consequence  of  their  local 
progress.  In  confirmation  of  this  it  may  be  mentioned  that  cachectic 
symptoms  usually  disappear  for  a  time,  after  the  removal  of  the  local 
disease.  It  is  well  known  that  the  constituent  cells  of  malignant  tumours 
are  remarkably  prone  to  degenerative  changes  ending  in  disintegration. 
It  seems  probable  that,  just  as  dissemination  depends  upon  the  entry  of 
living  tumour  cells  into  the  circulation,  so  cachexia  likewise  depends  upon 
the  entry  into  the  circulation  of  the  products  resulting  from  their  dis- 
integration. These  are  believed  to  comprise  toxic  albuminoids,  which, 
being  in  quantities  too  great  to  be  quickly  neutralized,  poison  the  system, 
especially  the  blood  and  haematopoietic  organs. 

Cachexia  is  more  frequently  seen  with  epithelioma  than  with  sarcoma, 
and  with  some  varieties  of  both  forms  of  malignant  disease — e.g.,  rodent 
ulcer,  spindle-celled  and  myeloid  sarcoma — it  seldom  occurs.  Even 
among  the  different  varieties  of  the  same  form  of  malignant  disease,  there 
are  great  divergencies  as  to  the  occurrence  of  cachexia  ;  thus  it  is  much 
more  frequently  met  with  in  association  with  cancers  whose  constituent 
cells  are  specially  prone  to  degenerative  disintegration  (e.g.,  the  ordinary 
cancer  of  the  breast),  than  with  those  whose  cellular  elements  are  more 
stable  (e.g.,  the  lip). 

A  similar  condition  is  sometimes  induced  by  very  large  non-malignant 
tumours,  especially  of  the  uterus  and  ovaries  ;  and  even  by  some  pseudo- 
plasms,  such  as  mycosis  fungoides. 

In  the  constitutional  changes  coincident  with  pregnancy  and  post- 
partuni  conditions,  we  see  manifested  the  physiological  counterparts  ot 
cachexia. 


8  THE  NATURAL  HISTORY  OF  CANCER 

It  follows  from  the  foregoing  analysis  of  the  distinctive  features  of 
^  malignancy,  that  there  is  nothing  new  or  specific  about  them  ;  these  effects 
may,  indeed,  be  ascribed  to  the  exacerbation  in  some  directions,  and  to 
the  diminution  in  others,  of  processes  which  are  of  normal  occurrence  in 
the  various  phases  of  embryonic  or  post-embryonic  life. 
*"  Thus  malignancy  is  a  relative  term,  of  which  there  is  no  absolute 
morphological  or  chemical  criterion.  Indeed,  malignancy — like  growth — 
has  no  specific  pathognomonic  mark  by  which  it  may  be  certainly  dis- 
X  criminated  and  appraised  ;  for — like  growth — malignancy  is  essentially  a 
dynamic  force,  whose  presence  can  only  be  surmised  and  estimated  by 
careful  weighing  of  the  ensemble  of  the  indications  available  for  its 
diagnosis — that  is  to  say,  by  its  effects. 

What,  then,  is  the  anatomical  element  upon  which  malignancy 
depends  ?  The  predominant  constituent  of  all  malignant  tumours  is  the 
cell,  and  it  is  to  the  cell  that  we  must  look  for  the  answer  to  this  question. 
Ever  since  the  discovery  of  the  cellular  nature  of  the  body,  the  cells  of 
malignant  tumours  have  been  closely  scrutinized,  with  the  hope  of  finding 
in  them  some  specific  mark,  but  all  in  vain.  The  more  thoroughly  the 
examination  has  been  made,  the  more  clearly  has  it  proved  the  correctness 
of  J.  Miiller's  conclusion  that :  "  The  minutest  elements  of  malignant 
tumours  do  not  differ  in  any  important  respect  from  the  constituents  of 
benign  tumours,  nor  from  those  of  the  body  in  its  adult  or  embryonic 
condition."  Such  being  the  case,  we  can  but  conclude  that  there  is  no 
specific  anatomical  element  or  chemical  substance  characteristic  of 
malignancy,  other  than  such  as  occur  in  the  physiological  state.  From 
this  it  may  be  inferred,  that  the  process  which  manifests  itself  in 
malignancy,  and  the  process  of  which  benign  tumours  are  the  outcome, 
are  the  same  in  kind,  and  that  they  differ  only  in  degree ;  while,  in  the 
normal  ontogeny,  both  have  their  physiological  prototypes. 

In  a  general  way,  it  may  be  said  of  malignant  tumours,  as  compared 
with  benign  ones,  that  they  are,  structurally  regarded,  characterized  by 
immaturity  and  defective  organization.  In  their  structure  cells  capable 
of  active  growth  and  development  predominate.  The  morbid  for- 
mation, however,  always  has  a  certain  likeness  to  the  structure  of  the 
part  whence  it  originates — hence  malignant  tumours  of  the  same  kind, 
but  springing  from  different  parts  of  the  body,  are  by  no  means  identical 
in  structure.  What,  for  instance,  can  be  more  divergent  in  this  respect, 
than  the  appearances  presented  by  microscopical  sections  of  cancers  from 
such  different  parts  as  the  breast,  the  stomach,  and  the  skin  ?  Moreover, 
if  we  pursue  the  analysis  further,  we  shall  find  that  even  special  substances 
secreted  by  the  cells  of  these  organs,  are  duly  represented  in  the  corre- 
sponding cancerous  products,  although  the  latter  are  never  able  to  produce 
a  perfect  secretion.  Thus,  more  than  half  a  century  ago,  J.  Miiller 
demonstrated  the  presence  of  casein  in  mammary  cancers,  and  the  special 
proneness  of  the  constituent  cells  of  these  tumours  to  fatty  metamorphosis 
is  well  known.  We  are  thus  reminded  of  the  similar  changes  that  the 
ells  of  the  normal  gland  undergo,  during  the  elaboration  of  their  peculiar 
secretion.  Of  similar  import  is  the  cornification  of  the  cells  of  cutaneous 
cancers.  Waring  has  specially  called  attention  to  this  neglected  feature 


INTRODUCTORY  9 

of  malignant  tumours  by  demonstrating,  that  the  constituent  cells  of 
cancers  of  the  stomach  and  pancreas  produce  the  same  special  ferments — 
pepsin,  trypsin  etc. — as  the  normal  secretory  cells  of  these  organs. 

With  regard  to  the  chemical  nature  of  malignant  tumours,  it  is 
noticeable  that  albuminoid  materials  predominate ;  and,  as  in  actively 
growing  structures  in  general,  sugar-forming  substances  abound. 

The  appearances  revealed  on  microscopical  examination  of  actively 
growing  parts  of  malignant  tumours,  on  the  whole,  have  a  great  likeness  to 
those  met  with  during  the  course  of  the  development  of  the  affected  part. 

In  the  case  of  cancers  of  glandular  origin,  the  epithelial  cells  at  the  seat 
of  disease  become  unduly  numerous,  and  acquire  a  multilaminar  arrange- 
ment, encroaching  on  the  lumen  of  the  gland,  which  they  commonly 
obliterate.  The  newly  formed  cells,  for  the  most  part,  also  often  lose 
their  typical  shape.  Thus  the  diseased  glandular  structure  is  converted 
into  a  club-shaped  mass  of  proliferating  epithelial  cells.  Here  and  there 
bud-shaped  collections  of  these  proliferous  cells  press  on  the  membrana 
propria,  forming  solid  processes,  which  interpenetrate  the  adjacent 
structures  in  the  directions  of  least  resistance,  where  they  branch  and 
anastomose.  By  the  repetition  and  further  extension  of  this  process  the 
cancerous  tumour  is  formed.  In  most  cases  these  ingrowing  epithelial 
columns  retain  their  solid  form ;  but  exceptionally  they  eventually 
develop  more  or  less  complete  lumina,  and  otherwise  mimic  the  structure 
of  the  gland  whence  they  originated. 

In  their  entirety,  the  pathological  appearances  present  striking  resem- 
blance to  those  observed  during  certain  stages  of  the  normal  ontogeny 
of  glands,  of  which  they  may  be  regarded  as  aberrant,  superinduced 
repetitions. 

Malignant  tumours  increase  by  the  continuous  growth  and  proliferation 
of  their  constituent  cellular  elements ;  and  the  indications  revealed  by  a 
thorough  study  of  the  minute  anatomy  of  these  cells  do  but  strengthen 
the  foregoing  conclusions.  Biologists  have  taught  us  the  important  part 
played  by  the  nucleus,  in  the  growth  and  multiplication  of  cells.  In  this 
connexion  it  is  significant  that  the  nuclei  of  the  cells  of  malignant  tumours 
are,  as  a  rule,  larger  and  richer  in  chromatin,  and  they  more  frequently 
originate  mitoses,  especially  asymmetrical  and  pluripolar  forms,  than 
their  physiological  prototypes.  Moreover,  it  has  lately  been  shown  that 
the  "  heterotype  "  mitosis,  which  is  believed  to  be  characteristic  of  gamic 
reproductive  cells,  is  also  a  special  feature  in  the  multiplication  of  the 
cells  of  malignant  tumours ;  but  of  this  more  anon.  These  deviations 
from  the  normal  are  but  the  morphological  expressions  of  a  high  degree 
of  proliferative  activity,  which  is,  indeed,  the  essential  characteristic  of 
the  cells  of  malignant  tumours,  and  the  source  of  all  their  special  qualities. 
Thus  the  vegetative  activity  of  cancer  cells  predominates  over  all  their 
other  functions  ;  and  it  is  in  this  special  dynamic  quality  that  the  essence 
of  malignancy  concentres.  Just  as  cells  embedded  in  the  stroma  of  an 
ovarium  become  ova  by  excessive  growth,  at  the  expense  of  adjacent  *)( 
nutritive  materials,  which  they  divert  from  other  cells  ;  so  we  may  infer 
that  those  cells  which  originate  malignant  neoplasms  become  different 
from  their  non-malignant  congeners  in  a  similar  way. 


10  THE  NATURAL  HISTORY  OF  CANCER 


The  Terms  "  Cancer,"  "  Epithelioma  "  (vel  Carcinoma),  and  "  Sarcoma." 

At  the  present  time  the  term  "  cancer  "  is  used  in  such  different 
senses,  that  it  is  necessary  for  those  who  employ  it  to  state  precisely  what 
they  mean  by  it.  In  the  popular  sense  every  malignant  tumour  is  a 
"  cancer  "  ;  but  in  medical  science  the  term  has  hitherto  usually  been 
restricted  to  certain  malignant  tumours — viz.,  to  those  of  epithelial 
origin,  for  which  the  scientific  equivalent,  according  to  the  accepted  system 
of  nomenclature,  should  be  epithelioma.1 

•  Owing,  however,  to  the  vogue  which  the  term  cancer  has  obtained  in 
the  vernacular,  as  the  synonym  of  malignant  tumour,  and  to  its  employ- 
ment in  this  sense  by  the  official  registrars  and  statisticians  of  all  modern 
communities,  it  seems  now  impossible  to  attach  to  this  term  any  other 
significance  than  that  sanctioned  by  popular  usage,  and  this  is  the  sense 
in  which  I  employ  it. 

We  are  indebted  to  J.  Miiller  for  the  fundamental  conceptions  on  which 
the  current  nomenclature  of  tumours  is  based.  He  first  enunciated  the 
important  principle,  that  the  structural  elements  of  every  tumour  have 
their  analogues  in  the  embryonic  or  adult  tissues  of  the  normal  organism. 
In  accordance  with  these  ideas,  the  different  kinds  of  tumours  have  been 
designated  by  adding  the  quasi-Greek  radical  a)^a  to  the  name  of  the 
corresponding  normal  tissues  whence  they  originate. 

Curiously  enough,  however, -in  discriminating  the  two  chief  varieties 
of  malignant  tumours,  this  method  has  seldom  been  rigidly  adhered  to  ; 
thus  malignant  tumours  of  epithelial  origin  have  been  commonly 
designated  "  carcinoma,"  and  those  of  connective-tissue  origin 
"  sarcoma." 

Etymologically  the  former  term  simply  means  crab-like  tumour 
(icap/civo?},  for  which  latter  the  Latin  equivalent  is  cancer.  The  ancients 
were  much  struck  by  the  crab-like  aspect  of  these  tumours,  but  whether 
this  fancied  resemblance  was  the  outcome  of  superficial  observation,  or 
of  profound  study  of  the  disease  by  dissection,  it  is  not  quite  clear.2 
Probably,  however,  they  knew  more  of  its  nature  and  its  "  roots,"  than 
we^commonly  credit  them  with.  At  any  rate,  the  term  "  carcinoma  " 
has  persisted  in  scientific  circles,  to  the  exclusion  of  its  more  appropriate 
rival  "  epithelioma." 

In  like  manner  the  term  "  sarcoma  "  is  also  exceptionally  derived. 
This  is  an  ancient  designation  formerly  applied  to  flesh-like  tumours  (adp^). 
Thus  Galen  says  :  "  We  call  sarcoma  a  fleshy  excrescence  prceter  naturam." 
There  was  naturally  much  diversity  of  opinion  as  to  just  what  should  be 
discriminated  as  flesh— hence  the  term  was  at  first  vaguely  used  (tumores 
carnosi  etc.).  Prior  to  the  discovery  of  the  cell  theory,  it  was  commonly 

'For  this  conception  as  to  the  origin  of  the  disease  we  are  indebted  to  Waldeyer  (1867) 
and  Ihiersch,  the  older  doctrine  as  to  the  connective-tissue  origin  of  malignant  epithelial 
tumours  by  metaplasia,  having  been  generally  abandoned 

Galen  says :  "  In  the  breasts  we  often  find  a  tumour  in  size  and  shape  closely  resem- 
bling the  animal  known  as  a  crab,  for  as  in  the  latter  the  limbs  protrude  from  either  side, 
so  in  the  tumour  the  swollen  veins  radiate  from  its  edges  and  give  a  perfect  picture  of 


INTRODUCTORY  11 

employed  as  synonymous  with  "  fungus."  Virchow  is  mainly  responsible 
for  the  rehabilitation  of  the  term,  and  for  its  modern  significance.  He 
described  as  sarcomata  new  formations  of  the  connective-tissue  type, 
distinguishable  from  the  corresponding  fully  evolved  tissues  by  their 
immaturity.  Subsequently  they  were  defined  as  tumours  of  embryonic 
connective  tissue,  or  of  some  of  the  modifications  that  this  structure 
undergoes  in  evolving  the  fully  developed  tissues. 


CHAPTER  II 
GEOGRAPHICAL  DISTRIBUTION  AND  INCIDENCE 

Preliminary  Apercu. 

AT  the  commencement  of  the  twentieth  century  the  great  problem  of 
the  causation  of  tumours,  like  a  gigantic  sphinx,  looms  large  on  the 
medical  horizon.  Of  this  problem  the  genesis  of  cancels  but  a  part, 
although  a  large  one.  Moreover,  it  is  important  to  recollect  that  these 
growths  are  not  peculiar  to  mankind,  nor  even  to  animals  ;  for,  as  I  have 
elsewhere  shown,1  similar  formations  affect  trees  and  other  vegetable 
organisms.  Indeed,  it  seems  clear,  as  I  long  ago  pointed  out,  that 
tumours  may  arise,  under  certain  conditions,  in  any  multicellular  animal 
or  vegetable  being. 

Another  important  consideration  is,  that  these  abnormalities  rarely 
arise  in  organisms  living  in  a  state  of  nature.  It  is  almost  exclusively 
among  domesticated  varieties,  among  those  that  have  been  kept  long  in 
confinement,  or  that  have  been  otherwise  abnormally  circumstanced, 
that  tumours  are  met  with.  Savages  and  wild  animals  are  very  rarely 
thus  affected ;  and  it  is  worth  noting  that  this  comparative  immunity  is 
very  marked  throughout  the  whole  of  the  monkey  tribe. 

In  a  general  way,  it  may  be  said  that  the  animal  world  is  much  less 
prone  to  malignant  and  other  tumours  than  humanity ;  and  this  appears 
to  me  to  be  due  to  the  fact  that  animals  have  been  much  less  extensively 
subjected  to  the  artificial  influence  of  domestication,  and  to  such  other 
abnormal  conditions  of  existence  as  I  have  above  referred  to,  than  man- 
kind. At  any  rate,  it  is  remarkable  that  nearly  all  the  examples  of 
animal  tumours  hitherto  reported,  malignant  and  otherwise,  have  been 
met  with  in  our  common  domesticated  species  ;  and  it  is  significant  that 
the  dog  is  the  animal  most  frequently  affected. 

Hitherto  progress  has  been  hindered  by  the  want  of  clear  conception 
as  to  the  nature  and  affinities  of  the  morbid  process.  Tumour  formation 
has  too  commonly  been  regarded  as  an  isolated  pathological  entity,  having 
no  connexion  with  other  biological  processes.  Yet  between  tumour  for- 
mation and  morphological  variation  in  general  there  is,  I  believe,  real 
affinity ;  and  in  ultimate  analysis  both  may  be  regarded  as  the  outcome 
of  the  cumulative  effects  of  changed  conditions  of  existence.  Of  these 
conditions  the  most  important  seem  to  me  to  be  changed  environment  and 
excess  of  food. 

"The  Principles  of  Cancer  and  Tumour  Formation,"  London,  1888,  p.  85  et  seq.  ; 
also  "Vegetable  Tumours  in  Relation  to  Bud  Formation,"  Trans.  Path.  Soc.  London, 
vol.  xxxviii.,  1887,  p.  460,  and  ibid.,  vol.  xl.,  p.  446.  Vide  also  Chapter  VI.  of  this  work. 

12 


GEOGRAPHICAL  DISTRIBUTION  AND  INCIDENCE         13 

As  I  have  indicated  in  my  work  on  the  "  Principles  of  Cancer  and 
Tumour  Formation,"  it  is  my  belief  that  factors  of  this  kind  play  a  leading 
part  in  the  causation  of  malignant  and  non-malignant  tumours.  Now 
that  the  fury  of  the  microbic  prepossession  has  somewhat  abated,  it  is  to 
be  hoped  that  these  neglected  biological  factors  will  receive  their  due 
recognition.  Changed  food,  changed  habits,  and  changed  environment 
are  as  potent  factors  in  pathogenesis,  when  they  tend  in  this  direction,  as 
they  are  in  physiological  evolution. 

Malignant  tumours  in  mankind  and  animals  consist  mainly  of  albu- 
minous or  proteid  substances ;  and  it  seems  not  unreasonable  to  suppose 
that  they  may  be  the  outcome  of  excess  of  these  substances  in  the  body, 
and  especially  of  such  of  them  as  serve  for  nuclear  pabulum.  When 
excessive  quantities  of  such  highly  stimulating  forms  of  nutriment  are 
ingested,  by  beings  whose  cellular  metabolism  is  defective,  I  believe  there 
may  thus  be  excited  in  those  parts  of  the  body  where  vital  processes  are 
most  active,  such  excessive  and  disorderly  proliferation  as  may  eventuate 
in  cancer.  However  this  may  be,  I  am  persuaded  that  the  ascertained 
facts  justify  the  belief,  that  there  is  a  certain  relation  between  the  con- 
ditions of  existence — in  which  alimentation  plays  an  important  part — 
and  the  incidence  of  cancer. 


Some  Generalities  as  to  the  Distribution  of  Cancer  among  Mankind. 

In  taking  a  comprehensive  survey  of  the  incidence  of  malignant 
tumours  as  they  affect  mankind,  it  is  important  to  note  the  wide  range 
of  these  maladies,  which  are  practically  ubiquitous. 

Another  striking  feature  in  this  connexion,  is  their  much  greater 
prevalence  in  some  localities  than  in  others.  Careful  study  of  these 
inequalities — which  although  persistent  are  not  permanent— has  con- 
vinced me  that  they  are  due  to  diversities  in  the  conditions  of  existence 
of  the  respective  populations,  as  I  shall  subsequently  have  occasion  to 
demonstrate. 

Those  who  have  travelled  among  savage  peoples  are  practically  unani- 
mous in  asserting,  that  malignant  tumours  are  very  rarely  met  with  under 
these  circumstances ;  but  in  most  modern  civilized  communities  diseases  of 
this  type  are  very  prevalent.  The  reputed  rarity  of  cancer  among 
uncivilized  people  is  fully  borne  out  by  the  reports  of  the  medical  officers, 
missionaries,  and  other  officials  who  have  resided  among  such  populations 
in  various  parts  of  the  world,  as  recorded  in  official  and  other  reports,  to 
which  I  shall  have  to  refer  more  in  detail  in  the  sequel.  There  seems  to 
me  to  be  no  warrant  for  Dr.  Bashford's  contention,  that  the  civilized 
and  the  savage  are  equally  liable,  and  that  the  differences  above 
indicated  are  merely  apparent. 

To  my  mind  it  has  been  clearly  established,  that  cancer  is  of  most 
frequent  occurrence  among  the  well-to-do,  highly  nourished  communities 
of  occidental  Europe ;  and,  within  the  limits  of  these  communities,  as  I 
have  proved,  the  disease  is  commonest  among  the  well-to-do  groups. 

Now,  if  I  were  asked  to  state  briefly,  the  chief  physical  difference 


14  THE  NATURAL  HISTORY  OF  CANCER 

between  savage  and  civilized  man,  I  should  unhesitatingly  reply  that  it 
consisted  in  the  latter  being  much  the  better  nourished ;  and  this  is  the 
conclusion  of  most  of  those  who  have  travelled  among  savages.  The  food- 
supply  of  the  latter  is,  indeed,  generally  irregular  and  precarious- 
occasional  gluts  alternating  with  long  spells  of  enforced  abstinence — and 
the  food  they  get  is  badly  cooked ;  whereas  the  former  have  constantly 
available  an  abundance  of  highly  nutritious  and  well-cooked  food. 

Thus,  speaking  of  the  natives  of  the  Gaboon  region  of  Equatorial 
Africa,  Du  Chaillu  says  :  "  No  wonder  they  are  so  fond  of  meat :  they  have 
it  so  seldom — i.e.,  only  when  they  can  get  it  by  hunting." 

From  indications  of  this  kind,  it  may  be  inferred  that  nutrition  and 
alimentation  play  an  important  part  in  cancer  causation,  as  I  shall 
subsequently  have  occasion  to  demonstrate  more  in  detail. 

It  has  been  noted  in  the  United  States,  in  Australia,  and  in  some  other 
communities,  that  immigrants  are  very  much  more  liable  to  malignant 
disease  than  are  the  native-born  population ;  and  that  they  experience  in 
their  new  homes  higher  cancer  death-rates  than  prevail  in  their  native 
countries.  Hence  it  may  be  inferred,  as  I  shall  indicate  more  fully  in 
the  sequel,  that  abrupt  change  of  environment  may  also  be  a  factor  in 
the  causation  of  this  disease. 

Race,  Complexion,  and  Conditions  of  Existence. 

In  human  beings,  well-marked  constitutional  peculiarities  and  morbid 
proclivities,  are  often  reputed  to  be  correlated  with  race  and  complexion. 
I  now  propose  to  inquire  whether  the  incidence  of  cancer  is  influenced  by 
factors  of  this  kind. 

So  far  as  present  indications  go,  it  appears  that  all  racial  varieties  of 
mankind  are  liable  to  malignant  tumours  ;  but  I  am  not  aware  of  any 
really  satisfactory  data,  as  to  the  relative  incidence  of  the  disease  among 
the  different  races.  From  such  information  as  is  available,  I  have  come 
to  the  conclusion  that  ethnological  factors  per  se  are  of  far  less  importance 
in  determining  the  incidence  of  cancer,  than  are  the  conditions  of  existence 
to  which  the  race  has  been  exposed.  I  have  arrived  at  this  conclusion 
mainly  from  studying  the  incidence  of  the  disease,  as  it  has  affected  such 
well-marked  racial  types  as  negroes,  North  American  Indians,  and  Jews. 

In  their  native  African  homes,  the  ancestors  of  the  negro  slaves  of 
the  United  States — like  other  similarly  situated  savages — are  believed  to 
have  been  almost  exempt  from  malignant  tumours.  Most  of  the  early 
writers  testify  as  to  this' comparative  immunity,  which  is  in  entire  accord 
with  what  we  now  know  as  to  the  present  condition  of  the  kindred  tribes 
in  Africa,  among  whom  cancer  is  very  rare,  as  I  shall  subsequently  have 
occasion  to  indicate  in  detail. 

Now,  in  Du  Chaillu' s  interesting  "  Travels  in  Equatorial  Africa,"  we 
have  an  admirable  account  of  the  modus  vivendi  of  these  tribes,  before 
contact  with  Europeans,  to  the  salient  features  of  which  I  have  previously 
alluded  as  determining  this  immunity. 

Transplanted  to  the  United  States,  and  having  lived  there  in  slavery 
for  over  two  centuries,  these  negroes  were  then  found  by  the  United  States 


GEOGRAPHICAL  DISTRIBUTION  AND  INCIDENCE         15 

authorities  to  have  acquired  greatly  increased  liability  to  cancer,  to 
which,  however,  they  were  very  much  less  prone  than  their  white  masters. 
Thus,  Chisholm's  statistics  show  that,  before  the  emancipation,  the  whites 
were  more  than  twice  as  liable  as  the  blacks,  and  this  was  specially 
noticeable  with  regard  to  uterine  cancer.  The  regimen  under  which  they 
lived  during  this  period,  has  been  well  described  by  Dr.  S.  Harris  l  as 
follows  :  The  planters  gave  their  slaves  the  best  hygienic  surroundings 
possible  ;  they  had  plenty  of  simple,  nutritious,  and  well-prepared  food, 
and  enough  out-of-door  labour  ;  sleep  and  recreation  were  well  regulated 
and  sufficient ;  they  were  \vell  clothed,  forced  to  keep  clean,  comfortably 
housed,  and  well  cared  for  in  sickness.  The  defective  and  unhealthy  were 
debarred  from  reproduction,  in  which  the  healthy  and  able-bodied  were 
encouraged  ;  in  short,  everything  was  done  to  promote  health,  vigour,  and 
long  life ;  and  under  this  system  the  slaves  multiplied,  and  had  splendid 
health — better,  in  fact,  than  that  of  their  white  masters.  Thus,  the 
Charleston  statistics,  from  1822  to  the  outbreak  of  the  Civil  War,  show 
that  the  general  death-rate  for  whites  was  25-98  per  1,000  living,  while 
that  for  blacks  was  only  24-04,  and  throughout  the  South  similar  con- 
ditions prevailed. 

After  thirty-five  years  of  freedom,  the  negroes'  health  is  found  to  have 
markedly  deteriorated  ;  they  now  experience  an  increased  general  mor- 
tality, with  greater  proclivity  to  nearly  all  kinds  of  disease,  especially  to  . 
tubercle,  pneumonia,  etc.  Even  their  reputed  comparative  immunity 
from  malaria  has  been  lost,  for  the  negro  death-rate  from  this  cause  now 
greatly  exceeds  that  of  the  whites.  Everywhere,  at  all  ages  and  in  both 
sexes,  these  negroes  now  have  greater  mortality  and  morbility  than  their 
white  compatriots  ;  and  they  have  become  a  short-lived  race.  Thus,  the 
Charleston  data  show  that  from  1865  to  1894  (i.e.,  after  emancipation) 
the  negro  general  death-rate  per  1,000  was  43-29,  against  only  22-7  for 
the  whites.2 

During  the  emancipation  period,  the  proclivity  to  malignant  tumours 
greatly  increased  among  negroes,  the  mortality  returns  for  1900,  showing 
a  death-rate  from  this  cause  of  48  per  100,000  living,  as  against  66-7  for 
whites.3  The  Louisville  City  Hospital  reports,  and  the  data  collected  by 
Matas  for  New  Orleans,  which  there  are  good  reasons  for  regarding  as 
more  reliable,  in  reference  to  this  particular,  than  the  national  statistics, 
show  that  malignant  tumours  are  now  as  common  there  in  negroes  as  in 
whites  (Rodman).  With  regard  to  uterine  cancer,  negresses  are  now 
more  prone  to  it  than  their  white  sisters,  the  respective  death-rates  for 
1900,  being  20  for  blacks  and  only  15-7  for  whites. 

Mammary  cancer  is  also  now  nearly  as  common  in  negresses  as  in 
white  women,  the  respective  death-rates  for  1900,  being  7-9  for  the  former 
and  9-1  for  the  latter.  Thus,  from  a  condition  of  comparative  immunity, 
these  negroes  have  now  become  nearly  as  prone  to  malignant  tumours  as 

1  American  Medicine,  September  7,  1901,  p.  375. 

2  The  Twelfth   United   States   Census  Report   for   1900,   gives   the  death-rates   for 
negroes  and  whites,  as  31 '8  and  17 '3  respectively. 

3  The  corresponding  figures  for  1890  are— blacks  36'65,  whites  53'93  ;  and,  for  1880, 
blacks  12-17,  whites  27'96. 


16  THE  NATURAL  HISTORY  OF  CANCER 

their  white  neighbours.  This  result  I  ascribe  to  sudden,  violent  alteration 
in  their  mode  of  life,  with  its  predominant  gluttony  and  laziness. 

In  like  manner,  the  North  American  Indians  are  believed  to  have  been 
almost  exempt  from  cancer  in  their  primitive  savage  condition  ;  but,  with 
the  altered  mode  of  life  consequent  on  contact  with  modern  civilization, 
this  comparative  immunity  has  now  to  a  large  extent  passed  away, 
although  they  are  still  less  prone  to  malignant  tumours  than  their  white 
compatriots. 

In  this  connexion  it  should  be  borne  in  mind,  that  in  their  primitive 
condition  these  savages  had  no  horses  and  no  firearms  ;  consequently  it 
was  no  easy  matter  for  them  to  kill  the  fleet  buffaloes,  on  which  they 
mainly  depended  for  subsistence  ;  hence,  in  their  primitive  condition, 
they  were  generally  less  well  nourished  than  when,  after  contact  with 
whites,  they  had,  by  the  acquirement  of  horses  and  firearms,  become 
assured  of  a  constant  supply  of  their  favourite  food. 

In  comparatively  recent  times  much  valuable  information  has  been 
forthcoming  as  to  the  incidence  of  disease  among  Jews,  the  general 
outcome  of  which  is  to  show  that  this  race  has  a  low  death-rate,  and  more 
than  average  longevity. 

Jews  suffer  less  than  most  races  from  tuberculous  disease  (especially 
phthisis),  pneumonia,  alcoholism,  diarrhoeal  affections,  and  some  other 
maladies ;  but  they  are  more  prone  to  diseases  of  the  nervous  system, 
especially  to  diabetes  and  insanity.  N. 

The  Jewish  race  being  widely  scattered  throughout  the  world,  and  the 
conditions  of  existence  of  its  various  communities  being  exceedingly 
diverse,  is  admirably  circumstanced  for  illustrating  the  comparative 
importance  of  race  factors  versus  conditions  of  existence,  in  determining 
the  incidence  of  cancer.  Unfortunately,  although  the  comparative 
pathology  of  the  Jew  has  been  fully  worked  out  for  most  diseases,  with 
regard  to  malignant  tumours,  the  data  are  scanty,  and  leave  much  to  be 
desired.  On  the  whole,  however,  the  available  indications  point  clearly 
to  the  conclusion,  that  the  liability  of  Jews  to  cancer  varies  with  their 
mode  of  life,  approximating  to  that  of  the  people  among  whom  they  dwell, 
but  generally  being  somewhat  inferior  to  it.  It  has  often  been  asserted 
that  persons  of  the  Jewish  race  are  very  rarely  affected,  but  this  is  evi- 
dently a  mistake.  In  the  United  States  J.  S.  Billings1  found,  that  the 
Jewish  cancer  mortality  was  about  the  same  as  that  for  the  rest  of  the 
white  population.  He  gives  the  cancer  mortality  per  1,000  deaths  as 
follows  : 

Jews.  Other  U.S.  Whites. 

Males         13-58     ..          ..     13'09 

Females 21'65     . .          . .     23'59 

Billroth's  experience  in  Vienna  was  somewhat  similar. 

Dr.  B.  W.  Richardson,  who  had  considerable  experience  among  the 
wealthy  Jews  of  West  London,  found  that  they  were  as  prone  to  malignant 
tumours  as  other  well-to-do  people  of  this  part  of  the  metropolis.  Referring 
to  the  alleged  great  rarity  of  this  disease  among  Jews,  he  says  : 2  "  I 

1  *enth  United  States  Census  Report  for  1880. 

2  Asclepiad,  vol.  viii.,  1891,  p.  145. 


GEOGRAPHICAL  DISTRIBUTION  AND  INCIDENCE         17 

regret  to  be  obliged  to  state  from  personal  knowledge,  that  the  Jewish 
community  is  by  no  means  exempt  from  cancer.  There  is  no  difference 
in  the  character  of  the  affection  in  the  Jew,  nor  any  selection  of  sex,  nor 
any  organic  selection.  With  the  Jews,  as  with  persons  of  other  races, 
women  are  most  liable  to  cancer,  but  I  have  witnessed  the  malady  in 
both  sexes.  I  have  known  Jewish  women  who  have  died  of  uterine 
cancer,  and  of  cancer  of  the  breast.  My  own  experience  is  amply 
sufficient  to  disprove  the  rash  assertion  of  Jewish  racial  exemption." 

An  anonymous  medical  man,  who  has  practised  for  twenty-five  years 
among  London  Jews,  recently  wrote1  as  follows :  "  There  is  undoubtedly 
an  impression  in  the  minds  of  the  members  of  the  Jewish  community 
that,  far  from  being  exempt,  the  Jews  are  especially  prone  to  suffer  from 
malignant  growths  ;  and  I  must  admit  that  I  have  been  somewhat  inclined 
to  share  this  view,  although  it  has  sometimes  appeared  to  me  that  cancer 
is  less  prevalent  now  among  them  than  it  was  in  my  earlier  experience." 

He  then  gives  some  statistical  data  based  upon  the  burial  returns  of 
the  United  Synagogues  of  London,  which  for  the  year  1900,  show  that 
2-3  per  cent.2  of  the  deaths  were  stated  to  be  due  to  cancer,  or  about 
one-half  the  ratio  for  England  and  Wales  in  general. 

Comparing  this  result  with  the  outcome  of  his  own  experience,  he 
says  :  "  It  is  impossible  that  there  is  not  some  fallacy  underlying  this 
immense  discrepancy  "  ;  and  he  thinks  that  the  explanation  of  this 
fallacy  is  to  be  found,  in  the  comparatively  large  number  of  children  and 
young  adults  believed  to  be  comprised  in  the  Jewish  population,  as  to 
which,  however,  there  is  no  clear  evidence. 

It  appears  to  me  that  the  author  of  this  instructive  communication 
has  failed  to  find  the  fallacy,  which  he  believes  underlies  his  statistics. 
It  is  hardly  likely  that  such  diversities  in  age  distribution  as  he  refers  to, 
will  account  for  such  considerable  disparities  as  his  data  show. 

The  really  important  part  of  the  fallacy  seems  to  me  to  consist  in 
this  :  that  unlike  things  have  been  compared  together.  The  great  bulk 
of  the  London  Jewish  population,  whence  these  data  are  derived,  is  an 
East-End  population,  living  under  conditions  of  stress  and  hardship ; 
whereas  the  average  Britisher  is  a  comparatively  prosperous  and  well- 
to-do  being.  To  get  a  correct  idea  of  the  relative  incidence  of  this  disease 
among  Jews  and  non-Jews,  only  populations  that  are,  roughly  speaking, 
similarly  conditioned  should  be  compared.  We  see  the  necessity  for  this 
in  the  fact,  that  the  cancer  mortality  of  West  London  is  so  much  higher 
than  that  of  the  East  End ;  and  this  was  the  case  before  the  present  Jewish 
immigration,  when  the  respective  populations  consisted  almost  entirely 
of  Britishers.  For  instance,  during  the  decennium  1881-1890,  the  cancer 
mortality  of  Stepney  was  only  3-7  per  10,000  living,  as  against  5-8  for  all 
England ;  and  at  still  earlier  periods  and  in  other  localities,  the  same 
disparity  is  apparent.  Even  when  correction  has  been  made  for  age  and 
sex  distribution,  and  for  deaths  in  public  institutions,  this  disparity  still 
remains ;  indeed,  in  the  poorest  parts  of  all  our  large  towns,  the  cancer 

1  British  Medical  Journal,  vol.  i.,  1902,  p.  681  ;  also  ibid.,  vol.  ii.,  1905,  p.  734. 

2  Estimated  to  be  equivalent  to  a  death-rate  of  5'2  per  1,000  living,  as  against  9'5  for 
London  in  general  (1899). 

2 


18  THE  NATURAL  HISTORY  OF  CANCER 

mortality  is  always  much  below  the  average.  Further,  in  Jewish  quarters 
in  London,  whether  rich  or  poor,  as  among  non-Jews,  the  cancer  mortality 
is  steadily  increasing. 

I  am  indebted  to  the  kind  intervention  of  Dr.  F.  L.  Hoffman,  the  well- 
known  statistician  of  the  Prudential  Insurance  Company  of  America, 
for  the  following  note  on  this  subject  by  Dr.  M.  Fishberg  of  New  York, 
who  has  specially  studied  this  subject  from  the  American  standpoint. 
He  says  :  *  "It  appears  from  all  the  available  data  that  cancer  is  by  no 
means  rare  among  Jews,  although  it  is  less  frequently  met  with  than 
among  non-Jews.  This  latter  condition  I  explain  as  due  to  the  fact  that 
cancer  of  the  uterus  and  female  breast  is  comparatively  rare  among  Jews  ; 
and,  as  is  well  knowTi,  the  two  last-mentioned  organs  are  the  very  ones 
most  frequently  affected  in  non-Jews.  On  the  other  hand,  cancer  of  the 
gastro-intestinal  tract  is  very  frequent  among  Jews  ;  thus,  nearly  45  per 
cent,  of  all  cases  of  malignant  disease  in  Jews  occurred  in  the  stomach, 
intestines,  liver,  pancreas,  rectum  etc.,  while  among  non-Jews  only  23  per 
cent,  of  the  patients  were  affected  with  cancer  of  these  organs.  Another 
point  is,  that  sarcoma  is  more  frequently  met  with  in  Jews  than  in 
Gentiles." 

With  regard  to  these  interesting  remarks,  my  own  impression  is  that 
it  has  not  yet  been  proved  that  Jewesses  have  any  special  immunity  from 
uterine  and  mammary  cancer ;  while,  as  to  the  gastro-intestinal  mani- 
festations of  the  disease,  I  have  found,  as  I  shall  subsequently  have  to 
indicate  in  detail,  that  more  than  half  of  all  cancers  in  Britishers  have 
this  localization. 

As  tending  to  confirm  the  belief  that  Jews  generally  experience  a 
some\vhat  lower  cancer  mortality  than  their  non-Jewish  compatriots, 
reference  may  be  made  to  an  instructive  publication  by  Dr.  F.  L. 
Hoffman,2  in  which  it  is  shown  that  in  the  United  States  those  of  Polish 
extraction — who  are  mostly  Jews — have  a  lower  death-rate  from  cancer 
and  tumour,  than  any  other  national  group  in  this  now  composite 
community. 

In  illustration  of  his  remarks,  he  cites  the  following  data,  showing 
the  comparative  mortality  from  these  diseases  of  the  various  nationalities 
per  100,000  of  population  : 


Aires. 

Native-born 
United  States 
Whites. 

Polish 
(mostly  Jews). 

German.                  Irish. 

Italian. 

45  to  64          .  .  I 
65  and  upwards 

155-3 
374-9 

92-3 
263-5 

238-6                232-2 
561-5                 479-9 

119-4 

392-7 

Dr.  W.  A.  King,  the  chief  statistician  of  the  Twelfth  United  States 
Census  Report,  referring  to  this  subject,  says  : 3  "  The  death-rates  per 

"Jewish  Encyclopaedia,"  vol.  iii.,  p.  529,  New  York,  1902:  to  which,  however,  I 
have  not  had  access. 

"  Race  and  Mortality,"  New  York  Examiner,  October,  1902,  p.  635. 
Twelfth  United  States  Census  Report  for  1900,  vol.  iii.,  part  i. 


GEOGRAPHICAL  DISTRIBUTION  AND  INCIDENCE         19 

100,000  of  white  population,  show  that  the  mortality  due  to  malignant 
tumours  was  highest  among  those  whose  mothers  were  born  in  France 
(92-8),  in  Scotland  (81-8),  and  in  Germany  (78-2)  ;  and  lowest  among 
those  whose  mothers  were  born  in  Russia  and  Poland  (25-7),  in  Italy 
(22-8),  and  in  Hungary  and  Bohemia  (31-5).  The  rate  was  lower  among 
those  whose  mothers  were  born  in  the  United  States  (48-3),  than  among 
those  whose  mothers  were  born  in  Ireland  (76-4),  or  in  England  and 
Wales  (72-0)." 

Here,  again,  it  will  be  noticed  that  those  of  Russian  and  Polish  extrac- 
tion, who  are  mainly  of  Jewish  race,  have  a  comparatively  low  cancer 
mortality. 

In  this  connexion,  however,  it  must  be  remembered  that  these  people 
are  among  the  poorest  in  the  United  States  ;  and  the  Italians,  who  share 
their  poverty,  also  share  their  comparative  immunity  from  cancer. 

The  lowest  cancer  death-rates  in  Austria  are  met  with  among  the 
Poles  of  Galicia  and  Bukowina,  who  are  largely  of  Jewish  origin  ;  and  in 
the  Prussian  provinces  bordering  on  Poland,  where  considerable  numbers 
of  Jews  are  met  with,  exceptionally  low  cancer  death-rates  prevail. 

The  idea  that  the  eating  of  pork,  per  se,  has  anything  to  do  with 
variations  in  the  incidence  of  the  cancer  mortality  may  certainly  be 
dismissed.  From  data  bearing  on  this  subject,  collected  by  Bauby1  in 
the  neighbourhood  of  Toulouse,  it  is  shown  that  those  who  eat  pork  are 
no  more  liable  to  cancer,  than  those  who  partake  of  other  kinds  of  flesh 
food. 

The  anonymous  correspondent  to  whose  publication  I  have  previously 
referred,  also  comes  to  this  conclusion.  He  says  :  "  At  the  present  time 
a  considerable  number  of  London  Jews  are  by  no  means  strict  adherents 
to  the  dietary  laws,  and  it  will  be  within  the  experience  of  every  one  who 
has  practised  among  them,  that  cancer  attacks  the  orthodox  in  this 
respect,  as  it  does  the  heterodox." 

As  a  general  rule,  I  think  it  will  be  found  that  the  Jewish  cancer 
mortality  has  very  little  to  do  with  race  or  with  racial  customs  per  se  ; 
but  that  it  varies,  according  to  the  conditions  of  existence,  in  different 
localities  and  countries. 

It  should,  however,  be  borne  in  mind  that  the  Jewish  race  is  of  oriental 
origin ;  and  even  now  Jews  retain  something  of  the  oriental  heritage  of 
abstemiousness  in  flesh-feeding,  as  compared  with  the  grossness  in  this 
respect  of  most  of  their  occidental  compatriots. 

Many  similar  facts  might  be  adduced,  showing  the  tendency  of  the 
cancer  mortality  to  vary  in  accordance  with  the  mode  of  life  of  individuals, 
rather  than  with  inherent  racial  peculiarities. 

The  United  States  census  reports  for  several  decades,  as  previously 
mentioned,  have  furnished  data  showing  the  comparative  cancer  mortality 
of  each  of  the  chief  racial  factors  contributing  to  its  composite  popula- 
tion. These  records  show  remarkable  differences  between  the  cancer 
proclivity  of  American-born  persons,  and  those  whose  mothers  were  born 
in  some  other  country.  Lyon  2  found  that  the  cancer  mortality  of  the 

1  Bulktin  Med.,  October  14,  1894. 

2  American  Journ.  Med.  Science,  vol.  xxviii.,  1901,  p.  640. 

2—2 


20  THE  NATURAL  HISTORY  OF  CANCER 

foreign-born  inhabitants  of  the  city  of  Buffalo  (1880  to  1899)  was  more 
than  4i  times  greater,  than  that  of  the  American-born  inhabitants.  In 
Australia  and  New  Zealand  similar  occurrences  have  been  noted,  as  I 
shall  subsequently  have  occasion  to  indicate.  Of  like  import  is  the 
converse  fact,  that  persons  of  British  descent  who  have  been  settled  for 
some  generations  in  the  United  States,  Australia,  and  New  Zealand,  then 
experience  a  much  lower  cancer  mortality  than  is  prevalent  in  their 
original  homes. 

Dr.  J.  Beddoe l  has  called  attention  to  the  further  fact,  that  although 
cancer  is  very  prevalent  in  Norway  and  Sweden2 — among  one  of  the 
blondest  populations  in  the  world,  comprising  less  than  5  per  cent,  of 
the  dark  type — it  is  of  the  greatest  rarity  in  Iceland  and  the  Faroe  Islands, 
which  are  inhabited  by  persons  of  the  same  race  as  the  Norwegians. 

According  to  Panum,  who  wrote  more  than  a  quarter  of  a  century 
ago,  cancer  was  then  almost  unknown  in  the  Faroe  Isles  ;  and  in  Iceland 
it  was  exceedingly  rare,  the  death-rate  from  this  cause  then  being  only 
7  per  100,000  (Hirst). 

Dr.  R.  Jeaffreson,  who  visited  these  islands  in  1892,  informed  me 
that  cancer  was  then  very  rare  there.  During  some  months'  residence  in 
the  Faroe  Isles  he  never  saw  a  single  case,  but  the  resident  doctors  told 
him  that  they  occasionally  met  with  an  instance — generally  in  half- 
breeds  or  Danish  immigrants.  In  Iceland  he  found  that  cancer  was  as 
exceptional  as  in  the  Faroes.  According  to  Dr.  Lazarus-Barlow,3  how- 
ever, the  disease  has  much  increased  of  late,  the  cancer  death-rate  for 
1900,  being  estimated  at  28-8  per  100,000. 

In  1890,  there  were  only  two  deaths  from  cancer  in  the  whole  of 
Iceland ;  but  in  1900,  twenty-two  of  such  deaths  were  notified. 

In  Greenland,  according  to  Panum,  malignant  tumours  are  of  great 
rarity. 

All  these  facts,  which  might  easily  be  multiplied,  point  clearly  to  the 
conclusion,  that  it  is  neither  race  nor  complexion  alone,  but  rather 
diversity  in  the  conditions  of  existence,  which  determines  the  incidence 
of  this  malady. 

The  Scandinavian  and  North  European  populations  are  mainly 
blonde,  and  they  have  a  very  high  cancer  mortality.  The  Italians  and 
South  Europeans  are  predominantly  dark  (70  per  cent.),  and  their  cancer 
mortality  is  much  below  the  average. 

In  this  country,  however,  I  have  convinced  myself  that  the  majority 
of  cancer  patients  are  of  the  dark  type ;  and  it  is  to  the  female  sex  that 
this  preponderance  is  chiefly  due.  Thus,  of  256  female  cancer  patients 
examined  by  me,  150  were  of  dark  and  106  of  fair  type.  In  order  to 
appreciate  the  significance  of  these  results,  it  must  be  borne  in  mind 
that  among  the  London  lower  classes,  whence  these  patients  were  derived, 
the  fair  type  decidedly  predominates,  Dr.  Beddoe's  estimate  being  57  per 
cent,  of  the  latter,  to  43  per  cent,  of  the  former.*  On  this  basis,  I  calculate 

1  Allbutt's  "  System  of  Medicine,"  vol.  i.,  1896,  p.  35. 

•  In  1900  the  cancer  death-rate  per  100,000  inhabitants  was  92. 

•  Arch.  Middlesex  Hosp.,  vol.  v.,  1905  p  275 
4  "  The  Races  of  Britain,"  1885. 


GEOGRAPHICAL  DISTRIBUTION  AND  INCIDENCE        21 

that  malignant  tumours  are  more  than  twice  as  frequent  in  dark  as  in 
fair-complexioned  individuals.  Here  mention  may  be  made  of  the 
curious  fact  that  I  have  never  met  with,  and  cannot  cite,  a  single  instance 
of,  malignant  disease  in  an  albino. 

In  this  connexion  it  may  also  be  noted,  that  the  stress  of  life  in  large 
towns  seems  to  exert  a  much  more  injurious  influence  on  the  fair-com- 
plexioned, especially  in  early  life,  than  on  those  of  darker  hue.  Owing 
to  this  cause,  it  is  believed  that  fair-complexioned  types  are  gradually 
being  supplanted  in  our  large  towns.  Changes  of  this  kind,  which  are 
very  subtle  and  far-reaching,  may  be  among  the  factors  contributing  to 
the  increased  cancer  mortality  of  modern  times. 

Finally,  it  may  be  here  mentioned  that  among  the  natives  of  India, 
Egypt,  Algeria,  Australia,  New  Zealand,  South  Africa,  Canada  *  etc., 
malignant  tumours  are  extremely  rare  ;  whereas,  among  the  white  people 
settled  in  these  localities,  tumours  of  this  kind  are  comparatively  common. 
Taken  in  conjunction  with  the  foregoing  considerations,  this  indication 
evidently  points  to  something  in  the  mode  of  living,  as  being  the  deter- 
mining aetiological  factor  in  cancer  genesis.  ' 


General  Survey  of  the  World-wide  Distribution  of  Cancer. 

In  every  part  of  the  world  the  incidence  of  cancer  presents  many 
variations.  Thus,  it  is  much  more  prevalent  in  some  countries  than  in 
others ;  and  within  the  limits  of  particular  communities — even  in  the 
smallest  administrative  areas — variations  of  this  kind  are  everywhere 
noticeable. 

I  have  previously  pointed  out  the  much  greater  frequency  of  the 
disease  in  civilized  than  in  savage  communities. 

As  a  general  rule,  malignant  tumours  are  of  much  commoner  occur- 
rence in  temperate  and  cold,  than  in  tropical  or  hot  regions. 

The  Danish  Government  report  that  cancer  is  not  unknown,  even  in 
the  Arctic  .regions  ;  but  no  definite  information  is  available  as  to  its 
incidence.  As  we  get  to  know  more  about  remote  localities,  it  will 
probably  be  found  that  no  settled  community  is  really  exempt. 

Although  it  is  improbable  that  any  tropical  community  is  really 
immune  from  malignant  tumours,  I  am  convinced  that  this  type  of 
disease  is  of  very  much  rarer  occurrence  among  tropical  people,  than 
among  the  inhabitants  of  the  temperate  regions,  and  especially  those  of 
occidental  Europe. 

I  shall  subsequently  adduce  abundant  evidence  from  many  parts  of 
the  world,  as  to  the  correctness  of  this  conclusion.  Here  I  can  only  offer 
a  few  remarks  on  the  general  aspect  of  the  question.  At  the  outset,  it 
must  be  mentioned  that,  with  the  exception  of  India  and  Brazil,  all  the 
chief  centres  of  civilization  are  situated  in  the  temperate  or  extra-tropical 
regions — e.g.,  Europe,  China,  Japan,  United  States,  British  North 
America,  Australia,  New  Zealand,  Cape  Colony  etc. 

In  Europe,  cancer  is  very  much  more  prevalent  than  in  any  of  the 

1  Formerly  also  among  the  Redskins — now  nearly  extinct — of  the  United  States. 


22  THE  NATURAL  HISTORY  OF  CANCER 

great  divisions  of  the  world  ;  indeed,  it  is  probable  that,  with  the  excep- 
tion of  China,  more  deaths  occur  from  this  cause  in  Europe  and  the  United 
States,  than  in  all  the  rest  of  the  world  together.  Moreover,  it  is  notice- 
able that  the  lowest  European  cancer  death-rates  are  found  along  its 
extreme  southern  fringe — i.e.,  the  shores  of  the  Mediterranean,1  com- 
prising the  Spanish,  Italian,  Austrian,  Turkish,  and  Grecian  littorals,  as 
well  as  the  adjacent  islands  (Sardinia,  Sicily,  Corsica  etc.). 

Although  we  have  no  statistical  data  as  to  the  prevalence  of  cancer 
in  Asia,  at  all  comparable  with  the  comprehensive  reports  issued  by  most 
European  Governments,  yet,  from  such  information  as  is  available,  it  is 
evident  that  this  disease  is  of  much  commoner  occurrence  in  the  great 
extra-tropical  empires  of  China  and  Japan,  than  it  is  in  the  essentially 
tropical  community  of  India.  With  regard  to  Northern  Asia,  no  informa- 
tion is  at  present  available. 

In  Australasia  cancer  is  everywhere  fairly  common  among  those  of 
white  descent,  who  are  congregated  in  the  extra-tropical  regions ;  but, 
among  the  aborigines,  it  is  so  rare  as  to  be  almost  unknown. 

It  seems  perfectly  clear  that  malignant  tumours  are  of  much  rarer 
occurrence  in  Africa,  than  in  any  other  of  the  great  divisions  of  the  world  ; 
and  most  of  this  vast  continent  is  tropical,  with  the  exception  of  Cape 
Colony  and  its  vicinity.  It  is  only  in  this  extra-tropical  region  that 
cancer  is  at  all  common  ;  and  even  here,  it  is  those  of  white  descent  who 
are  the  chief  sufferers,  for  the  natives  are  seldom  affected. 

In  the  American  Continent  cancer  is  much  more  frequent  in  its  northern 
or  temperate  part  than  elsewhere.  Thus,  this  malady  is  common  in  all 
parts  of  British  North  America,  except  among  the  aborigines.  It  is  the 
same  in  the  United  States,  where,  moreover,  the  cancer  mortality  of  the 
Northern  States  is  more  than  double  that  of  the  Southern  ones. 

In  Mexico  and  the  Central  American  communities,  cancer  is  decidedly 
rarer  than  in  the  United  States.  According  to  Jourdanet,  it  is  almost 
unknown  in  the  hot  regions  of  Mexico ;  whereas  in  the  cool  regions,  on 
the  high  plateaux,  it  is  frequent. 

In  the  tropical  regions  of  South  America,  of  which  Brazil  is  the  great 
exemplar,  cancer  is  rarer  than  in  any  other  part  of  the  American  Continent; 
and  in  Brazil,  according  to  Sodre,  the  malady  is  rarest  in  the  equatorial 
regions,  increasing  in  frequency  with  remoteness  from  the  equator.  It 
accords  with  this,  that  cancer  is  much  more  frequent  in  the  Argentine 
Republic  and  in  Uruguay,  than  in  Brazil. 

How  is  the  much  greater  prevalence  of  malignant  tumours  in  tem- 
perate than  in  hot  climates,  which  this  world- wide  survey  reveals  to  be 
accounted  for?  Races,  says  Hippocrates,  "are  the  daughters  of 
climates";  but,  as  I  have  previously  shown,  diversities  of  this  kind 
cannot  be  explained  by  racial  peculiarities.  The  influence  of  climate 
per  se,  is  as  impotent  as  race  per  se,  to  solve  this  problem.  Thus,  it  is 
only  in  the  conditions  of  existence,  that  an  adequate  solution  can  be 


uoitdTv^n!  t?<Peni.ker>  the  Mediterranean  littoral-from  Gibraltar  to  the  Tiber-is 

SSttSttSttSStettZttTE^ 


GEOGRAPHICAL  DISTRIBUTION  AND  INCIDENCE        23 

found  ;  and  in  this  connexion  climate  is  no  doubt  a  powerful  factor.  Thus 
regarded,  the  greater  variability  of  the  temperate  as  compared  with  the 
tropical  climates,  is  probably  quite  as  important  as  the  lower  average 
range  of  temperature.  The  greater  bulk,  muscularity,  activity,  and 
superior  physical  endowment  of  the  people  of  temperate  climates,  as 
compared  with 'their  tropical  counterparts,  may  be  mainly  ascribed  to 
the  former  cause,  which  favours  more  active  tissue  changes ;  and  so 
creates  the  desire  for  a  highly  stimulating  and  nutritious  diet,  which 
finds  its  expressions  in  a  predominantly  carnivorous  alimentation.  On 
the  other  hand,  tropical  people,  with  their  less  variable  climates,  are 
remarkable  for  their  extreme  frugality  in  living,  their  open-air  existence, 
and  their  predominantly  vegetarian  diet.  It  is  a  remarkable  fact,  but 
nearly  all  tropical  people  manifest  decided  aversion  for  a  too  carnivorous 
diet ;  and  this  cannot  be  ascribed  to  backward  civilization,  but  it  is  rather 
due  to  recognition  of  the  fact,  that  much  animal  food,  in  hot  climates, 
predisposes  to  ill-health  and  disease.  The  great  precocity  of  growth  and 
development  in  tropical  populations,  with  the  correlated  premature 
senility,  the  high  general  and  infantile  mortality — which  greatly  exceeds 
that  of  Europe,  often  to  the  extent  of  being  more  than  double — and  the 
consequent  short  duration  of  life  :  all  of  these  effects  are  probably  chiefly 
consequent  on  a  high  range  of  temperature  ;  while  to  this  factor  may 
also  be  ascribed  the  early  sexual  maturity,  and  the  great  reproductive 
activity  which  is  so  noticeable. 

Such  is  the  direction  in  which,  as  it  seems  to  me,  the  answer  to  our 
question  must  be  sought. 

"  How  vast,"  says  Sir  R.  Giffen,  "  must  be  the  economic  gulf  separat- 
ing the  people  of  Great  Britain  from  India  and  like  parts  of  the  Empire, 
when  we  find  that  42,000,000  of  people  in  the  United  Kingdom  consumed 7< 
in  food  and  drink  alone,  an  amount  equal  to  the  whole  income  of  over 
300,000,000  of  people  in  India." 

In  the  same  strain  Meredith  Townsend,  one  of  the  latest  and  best 
exponents  of  Indian  life,  writes  :  "  There  is  no  abstemiousness  in  the 
world,  and  no  thrift,  like  the  thrift  and  the  abstemiousness  of  the  average 
native  of  India.  .  .  .  Millions  of  men  in  India,  especially  on  the  richer 
soils  and  in  the  rice  deltas,  live,  marry,  and  rear  healthy  children  upon 
an  income  which,  even  when  the  wife  works,  is  rarely  above  two  shillings 
a  week,  and  frequentty  sinks  to  eighteenpence." 

The  natives  of  India  live  on  millet  or  rice,  a  little  milk,  with  the 
butter  from  the  milk,  and  the  vegetables  they  grow  ;  and  of  these  they 
partake  sparingly.  They  seldom  eat  any  meat.  It  is  only  the  Brahmins, 
the  priestly  caste,  who  form  but  a  small  fraction  of  the  immense  Hindoo 
population,  who  never  eat  any  flesh  food.  The  immense  majority  of  the 
people  live  a  rural  life,  depending  upon  agriculture  for  their  subsistence. 
Such  are  the  conditions  of  existence  in  India  ;  and  India  is  typical  of  the 
tropics. 

Now  contrast  the  tropical  mode  of  living  with  that  prevalent  in  our 
country,  where  all  the  conditions  are  so  different ;  where  the  average  wage 
of  the  worker  amounts  to  thirty-eight  shillings  a  week ;  and  where  the 
alimentation  comprises  a  meat  consumption  of  over  130  pounds  per  head 


24  THE  NATURAL  HISTORY  OF  CANCER 

per  year,  together  with  an  abundance  of  other  highly  nutritive  proteid 
food  products,  fats  etc. 

Moreover,  it  is  in  the  tropics  that  the  human  race  is  believed  to  have 
originated,  and  there  the  anthropoid  apes,  our  nearest  animal  connexions, 
who  are  mainly  vegetarians,  still  flourish  ;  and  are  seldom,  if  ever,  affected 
with  malignant  tumours. 

It  is  to  conditions  such  as  these  and  their  consequences,  as  I  shall 
often  have  occasion  to  point  out  in  the  sequel,  that  the  greater  prevalence 
of  malignant  tumours  in  temperate,  than  in  tropical  countries,  must  be 
ascribed. 

Unlike  certain  specific  infective  diseases,  such  as  malaria,  with  which 
cancer  has  often  been  compared,  this  malady  is  not  limited  to  definite 
localities,  but  is  practically  ubiquitous.  Ubiquity  differentiates  cancer 
from  all  parasitic  maladies,  for  even  tubercle  is  far  less  ubiquitous  than 
cancer.  Cancer  and  tubercle  centre  in  temperate  climates,  whereas 
malaria  is  the  predominant  malady  of  the  tropics. 

Tumours — including  the  malignant  kinds — seem  to  me  to  be  more 
akin  to  malformations  per  excessum,  than  to  specific  endemic  maladies. 
The  congenital  origin  of  many  tumours,  malignant  and  otherwise,  testifies 
against  their  parasitic  origin.  Malformations  and  other  morphological 
variations,  like  tumours,  are  found  in  all  localities,  climates,  and  races  ; 
and  it  is  specially  noticeable  that,  like  tumours,  they  are  much  commoner 
in  civilized  humanity  than  in  savages ;  and  in  domesticated  animals, 
as  well  as  in  those  that  have  been  kept  long  in  confinement,  than  in 
animals  accustomed  to  a  less  artificial  environment.  Here  it  may  be 
mentioned,  that  the  prevalence  of  defects  of  this  kind  has  greatly 
increased  in  our  country  during  the  last  half-century. 


General  Survey  of  the  Distribution  of  Cancer  in  Europe. 

Statistical  records  show  that  malignant  tumours  are  very  much  more 
prevalent  in  Europe,  than  in  any  other  of  the  great  divisions  of  the  world ; 
and  it  is  specially  in  the  northern  and  central  parts  of  this  Continent  that 
the  cancer  mortality  is  so  terribly  high.  In  Southern  Europe  the  inci- 
dence of  the  disease  is  much  less,  and  I  have  previously  referred  to  its 
special  rarity  along  the  Mediterranean  littoral. 

Although  the  official  reports  of  different  countries  are,  in  some  respects, 
not  always  strictly  comparable,  yet  the  following  data  may  be  taken  as 
giving  a  fairly  accurate  notion  as  to  the  comparative  incidence  of  the 
disease.  The  figures  show  the  cancer  death-rates  per  100,000  living  for 
the  year  1900,  unless  otherwise  stated. 

The  maximum  incidence  of  the  disease  seems  to  be  in  Switzerland, 
where,  according  to  Nencki,  the  cancer  death-rate  for  the  year  1898  was 
132,  and  for  the  decennium  1895-1904  it  has  been  estimated  at  128. 

In  Denmark  the  malady  appears  to  be  nearly  as  rampant  as  in  Switzer- 
land, for  the  cancer  death-rate  for  all  the  towns,  for  the  years  1892-1897 
averaged  130. 

France  comes  next  with  a  cancer  death-rate  of  104,  for  all  towns  of 


GEOGRAPHICAL  DISTRIBUTION  AND  INCIDENCE         25 

above  3,000  inhabitants ; 1  and  is  closely  followed  by  Sweden,  with  a 
cancer  mortality  of  102  for  its  town  population. 

The  figures  for  the  other  countries  are  as  follows  :  Holland,  93  ; 
Norway,  92 ;  England  and  Wales,  82  ;  Scotland,  80 ;  Germany,  71 
(Prussia,  59 ;  Bavaria,  98 ;  Baden,  101 ;  Saxony,  95  ;  Wurtemburg,  93)  ; 
Austria*  70  ;  Ireland,  61  ;  Italy,  52  ;  Spain,  39  ;  Belgium,  36  (1880-1887) ; 
and  Hungary,  33. 

As  to  Russia,  no  satisfactory  data  are  available,  but  the  disease  seems 
to  be  everywhere  fairly  prevalent. 

In  Greece,  Turkey,  and  the  Balkan  countries,  cancer  is  believed  to  be 
rare,  but  hardly  any  recent  information  is  available  ;  2  and  with  regard  to 
Portugal  it  is  the  same. 

Along  the  Mediterranean  littoral,  as  previously  mentioned,  some  of 
the  lowest  cancer  death-rates  in  Europe  are  to  be  found.  Thus,  on  the 
Spanish  coast,  the  figure  for  the  province  of  Almeira  is  25,  that  for 
Valencia  28,  for  Genoa  the  same,  for  Alicante  29,  while  the  figures  for 
Andalusia  and  Catalonia  are  equally  low.  Among  the  natives  at 
Gibraltar  the  cancer  death-rate  is  25,  and  at  Malta  the  disease  is 
reported  to  be  very  rare  among  the  natives.3  On  the  French  coast, 
the  cancer-mortality  is  everywhere  much  below  the  French  average ; 
but  precise  data  are  only  available  for  the  towns,  and  of  these  Marseilles 
has  the  lowest  cancer  death-rate  of  any  large  town  in  France — viz.,  69. 
In  Corsica  the  disease  is  very  rare,  the  figures  for  the  chief  towns  being 
32  (1895).  In  Sardinia  the  cancer  death-rate  is  only  19,  and  in  Sicily 
34.  On  the  Italian  coast  the  figure  for  Calabria,  for  Basilicata,  and  for 
Apulia  is  30,  and  for  Abruzzie  Molise  35.  On  the  Austrian  littoral,  the 
cancer  death-rate  for  Croatia  is  16,  and  for  Dalmatia  19. 

An  examination  of  this  list  shows,  that  malignant  tumours  are  of  most 
frequent  occurrence  in  those  communities  where  the  inhabitants  are  pre- 
dominantly well-to-do ;  and  where  they  now  are,  and  for  some  time  have 
been,  exceptionally  well  nourished.  At  first  sight,  it  might  be  thought 
that  such  a  description  hardly  applies  to  the  countries  at  the  head  of  my 
list,  for  the  aggregate  wealth  of  Switzerland  and  the  Scandinavian 
countries  is  comparatively  inconsiderable.  It  must,  however,  be  borne 
in  mind  that  these  communities  have  no  paupers  and  no  millionaires  ; 
and  a  careful  examination  of  the  subject  reveals  the  fact  that  their 
average  of  well-being  is  higher  than  elsewhere  in  Europe,  as  is  indicated 
by  their  exceptionally  low  general,  infantile,  and  tuberculous  death- 
rates.  In  fact,  vital  statistics  show  that  the  inhabitants  of  these  countries 
are,  on  the  average,  the  healthiest  and  best-nourished  people  in  Europe. 

Very  different  conditions  of  existence  prevail  where  the  lowest  cancer 
death-rates  are  found.  Here  the  people  are  predominantly  poor,  of 
necessity  very  frugal,  subsisting  on  an  alimentation  which  comprises  but 
little  proteid  food ;  and  these  conditions  are  chronic. 

The  attempt  to  explain  these  diversities  as  due  to  inequalities  in  the 

1  Comprising  only  about  one-third  of  the  entire  population. 

2  For  Servia  (1895  to  1904)  the  cancer  death-rate  has  been  estimated  at  8  per  100,000 
living  ;  the  phthisis  death-rate  being  245. 

3  Boudin  states  that  3,200  deaths  among   the   indigenes   (1822-34)  comprised  not 
a  single  cancer  death. 


20 


THE  NATURAL  HISTORY  OF  CANCER 


age  and  sex  distribution  of  the  respective  populations  has  completely 
failed,  wherever  the  requisite  data  for  making  such  corrections  have  been 
available ;  and,  primd  facie,  it  is  obvious  that  such  diversities  as  those 
above  indicated,  are  far  too  marked  to  be  explained  in  this  way. 

Here  it  may  be  noted  that  the  people  of  Europe  now  are,  and  for  a 
long  time  have  been,  on  the  average,  better  nourished  than  those* of  any 
of  the  other  great  divisions  of  the  world. 

In  plenty  the  Hydra  buds,  in  less  favourable  circumstances  it  repro- 
duces sexually.  Mankind,  under  similar  circumstances,  as  I  have  indi- 
cated in  my  work  on  the  "  Principles  of  Cancer  and  Tumour  Formation," 
is  apt  to  be  affected  in  an  analogous  way.  Here  the  gemmation  manifests 
itself  as  tumour  formation,  which  may  be  regarded  as  reversion  from 
dominant  sexuality,  to  a  more  or  less  incomplete  attempt  at  agamogenesis. 
In  ultimate  analysis,  then,  both  gemmation  and  tumour  formation  may 
be  ascribed  to  what  Geddes  calls  predominant  anabolism.  The  more 
thoroughly  the  cancer  problem  is  studied  in  its  ensemble,  the  more  manifest 
this  inter-relation  becomes. 

The  following  remarkable  data  by  Bertillon,  showing  the  comparative 
fertility  of  the  well  nourished  and  of  the  poorly  nourished,  is  of  much 
interest  in  this  connexion  : 

TABLE  SHOWING  BIRTHS  PER  1,000  WOMEN— AGED  15  TO  50— PER  ANNUM, 
IN  DIFFERENT  QUARTERS  OF  LONDON,  PARIS,  BERLIN,  AND  VIENNA. 


Classes  of  Population. 

Average. 

London. 

Paris. 

Berlin.       1      Vienna. 

Very  poor 

153 

147 

108 

157                200 

Poor           

132 

140 

95 

129                164 

Comfortable          ..          ...  j        112 

107 

72 

114                155 

Very  comfortable 
Rich           

105 

78 

107 

87 

65 
53 

96                153 
63                107 

Very  rich 

51 

63 

34 

47                 71 

This  antagonism  between  individuation  and  reproduction  long  ago 
secured  recognition  in  the  homely  adage,  "  The  rich  for  luck,  and  the 
poor  for  children  ";  and  in  this  connexion  Adam  Smith  called  attention 
to  the  poor  half-starved  Highland  crofter  women,  with  their  families  of 
twenty  or  more  children. 

I  shall  often  have  occasion  to  refer  to  these  fundamental  etiological 
conceptions  in  the  sequel,  but  for  the  present  these  brief  introductory 
remarks  must  suffice. 

It  accords  with  the  foregoing  that  the  cancer  mortality  of  the  capital 
cities  and  great  towns,  where  the  wealth  of  the  nations  is  clotted,  is 
generally  above  the  average  ;  while  in  rural  districts  the  disease  is  less 
prevalent  than  in  towns,  although  there  are  here  some  exceptions.  There 
can  be  no  doubt  that  the  town  people,  owing  to  their  greater  earning 
capacity,  are,  as  a  rule,  better  nourished  than  the  rural  inhabitants ; 
although  the  great  inequalities  in  the  distribution  of  wealth,  which  are 
specially  prevalent  in  urban  communities,  with  their  paupers  and  mil- 
lionaires, often  neutralize  this  effect. 


GEOGRAPHICAL  DISTRIBUTION  AND  INCIDENCE         27 

The  cancer  death-rates  for  the  chief  European  capitals  for  1900,  were 
as  follows  :  Copenhagen,  139  ;  Stuttgart,  127  ;  Dresden,  125  ;  Vienna,* 
121  ;  Munich,  119  ;  Edinburgh,  116 ;  Stockholm,  110 ;  Berlin,  109 ; 
Paris,  105  ;  Berne,  105  (with  canton)  ;  St.  Petersburg,  100  ;  Amsterdam, 
98  ;  London,  96  ;  Dublin,  93  (with  county)  ;  Prague,  85  ;  Madrid,  78  ; 
Rome,  77  ;  Buda-Pest,  72  ;  Ghristiania,2  66  ;  and  Brussels,  44. 

In  Constantinople,  Athens,  and  the  capitals  of  the  Balkan  States,  the 
disease  is  said  to  be  comparatively  infrequent,  but  no  recent  data  are 
available. 

For  the  chief  European  towns  the  corresponding  rates  are  as  under  : 

Geneva,  177  ;  Rouen,  173  ;  Lyons,  153  ;  Florence,  137  ;  Reims,  132 
(1895) ;  Danzig,  122  (1895) ;  Ravenna,  120  (1887-1899) ;  Strassburg,  118  ; 
Keil,  113  ;  HaUe,  112  ;  chief  Danish  towns,  111  ;  Breslau,  109  ;  Dundee, 
107  ;  Venice,  103  ;  Milan,  101  ;  Trondhjem,  99  ;  Utrecht,  97  ;  Hamburg, 
97  (1898)  ;  Bordeaux,  97  ;  Aberdeen,  95  ;  Cologne,  91  ;  Hague,  90  ;  Rotter- 
dam, 90  ;  Birmingham,  85  ;  Seville,  85  ;  Glasgow,  82  ;  Bremen,  81  (1875- 
1878)  ;  Malmo,  80  ;  Manchester,  78  ;  Liverpool,  77  ;  Marseilles,  69  ; 
Dusseldorf,  61  ;  Genoa,  59  (1887-1899)  ;  Turin,  59  (1,887-1899)  ;  Naples, 
56  (1899)  ;  Barcelona,  53  ;  Valencia,  39  etc. 

Some  of  the  highest  cancer  death-rates  known  to  me  have  been  met 
with  in  small  villages  of  Normandy — viz.,  Oulchy,  400  ;  St.  Sylvestre,8 
363  (1880-1887)  ;  Rocroi,  266  ;  and  Cormeilles,  203.  In  this  part  of 
Normandy  cancer  is  more  prevalent  than  in  any  other  district  of  France 
— viz.,  for  the  departments  of  Eure  et  Loire  167,  and  for  1'Aisne  161 
(1900).  A  very  high  cancer  mortality  is  also  reported  at  Cracow,  316 
(1887-1898)  ;  Erlangen,  250  ;  and  in  the  canton  of  Lucerne,  204  (1898). 

With  these  phenomenally  high  rates,  it  is  interesting  to  compare  the 
following  exceptionally  low  ones — viz.,  Croatia  and  Sclavonia  (provinces 
of),  16  ;  Valais  (canton  of),  16  (1898)  ;  Shetland  Isles,  16  (1874)  ;  Cagliari, 
18  (1887-1891)  ;  Dalmatia  (province  of),  19  ;  Sardinia,  19  ;  Ajaccio,  19  ; 
Corti,  20  ;  Oviedo  (province),  21  ;  Kerry  (county),  27  etc. 

It  has  long  been  a  moot  question  whether  malignant  tumours  are  of 
more  frequent  occurrence  in  urban  or  in  rural  districts ;  and  even  in 
modern  times,  with  the  aid  of  statistical  data,  the  answers  given  to  this 
question  are  not  always  unanimous. 

Unfortunately,  the  English  national  statistics,  so  excellent  in  most 
respects,  contain  no  data  bearing  directly  on  this  important  subject ; 
but,  from  such  crude  information  as  can  be  indirectly  gleaned,  it  appears 
that  at  the  present  time  the  disease  is  as  frequent  in  the  rural  districts 
as  in  the  towns. 

As  long  ago  as  1838,  William  Farr  investigated  this  subject,  and  found 
that  the  cancer  deaths  in  the  rural  districts  were,  to  those  in  the  towns, 
in  the  ratio  of  1  to  0-97.  Walshe  soon  afterwards,  basing  his  calculation 
on  information  contained  in  the  Registrar-General's  reports  for  the  years 
1838-1841  (which  comprised  the  metropolis  and  twenty-five  towns  on  the 
one  hand,  and  a  number  of  rural  districts  on  the  other),  found  that  the 
cancer  mortality  in  the  rural  districts  then  was  19-8  per  100,000  living, 
and  in  the  towns  18-3. 

1  Exclusive  of  sarcoma.  2  And  district.  3  Population  379. 


28  THE  NATURAL  HISTORY  OF  CANCER 

When  these  estimates  were  made,  65  per  cent,  of  the  population  lived 
in  the  country.  Now,  however,  such  has  been  the  rapid  increase  of 
urbanization,  only  23  per  cent,  of  the  population  dwell  in  the  country, 
and  of  these  a  large  proportion  really  belong  to  the  towns  in  whose 
suburbs  or  vicinity  they  reside.  Indeed,  so  thoroughly  urbanized  is  the 
country  at  the  present  time,  that  differential  vital  statistics  as  between 
town  and  country  have  lost  much  of  their  significance. 

Tatham  has  investigated  this  subject,  on  the  basis  of  the  statis- 
tical data  for  the  year  1901.  He  found  that,  at  ages  above  thirty-five, 
the  crude  and  corrected  (for  sex)  cancer  mortality  per  100,000  living,  in 
urban  and  rural  districts,  was  as  follows  : 

Crude  Rate.  Corrected  Rate. 

Urban          246     ..          ..260 

Rural  268     ..          ..234 

In  Scotland,  where  for  many  years  the  national  statistics  have  been 
kept  in  such  a  way  as  to  facilitate  comparisons  of  this  kind,  cancer  is 
more  prevalent  in  the  towns  than  in,  the  country  ;  but  the  distinctions 
are  not  very  marked,  probably  because  the  Scotch  people,  like  the 
English,  have  been  so  completely  urbanized — over  75  per  cent,  of  them 
being  massed  in  the  towns — that  few  parts  of  the  country  are  exempt 
from  urbanizing  influences.  Cancer  is  least  prevalent  in  the  islands, 
where  the  conditions  are  purely  rural,  the  people  are  poor,  and  the  alimen- 
tation is  mainly  vegetarian. 

The  following  figures  showing  the  cancer  death-rates  illustrate  this  : 

1905.  1900.  1891.  18SS. 

Principal  towns       ....         92         ..         84  70  63 


Large  towns  . .  . .  80  .  70 

Small  towns  . .  . .  79  .  77 

Midland  rural  districts  . .  99  .  83 

Insular  rural  districts  . .  79  .  56 

Average  for  all  Scotland  . .  89  .  81 


Ireland  is  the  least  urbanized  and  poorest  part  of  the  United  Kingdom, 
and  it  accords  with  the  foregoing  indications  that  it  is  also  the  least 
prone  to  cancer  ;  and  when  the  corresponding  cancer  death-rates  have 
been  corrected  for  diversities  in  age  and  sex  distribution,  this  comparative 
immunity  is  seen  to  be  even  more  marked  than  it  at  first  appeared  to  be. 

The  highest  Irish  cancer  mortality  is  met  with  in  well-to-do  Ulster, 
which  comprises  the  large  city  of  Belfast,  where  the  population  is  largely 
of  Scotch  descent  and  of  Scotch  habits  ;  but  the  rural  division  of  Armagh 
has  the  highest  cancer  death-rate— viz.,  104  (1897-1901).  Next  in  order 
come  the  counties  of  Dublin  (84)  and  Londonderry  (82),  each  comprising 
a  large  town  ;  while  the  lowest  rates  are  in  the  wild  and  poverty-stricken 
West-in  Kerry  (26),  Mayo  (36),  and  Clare  (38),  the  figures  being  for  the 
period  1897-1901. 

The  French  statistics  1  illustrate  similar  conditions  in  a  very  striking 
way,  although  they  give  no  information  for  the  rural  districts,  except  as 

-R»  Vif°r  rTT1,1  °fficial  Publications  relating  to  this  matter,  I  am  indebted  to  M.  le  Dr.  J. 
^ertillon,  Lhef  des  travaux  statistiques  de  la  ville  de  Paris ;  and  to  M.  Monod,  Directeur  de 
1  Assistance  et  de  1'hygiene  publiques,  to  both  of  whom  I  tender  my  thanks 


GEOGRAPHICAL  DISTRIBUTION  AND  INCIDENCE 


29 


to  the  small  towns  known  as  chefs-lieux  d'arrondissement. 
years  1895  and  1900,  the  figures  were  as  follows  : 

1895. 

Paris             119 

All  towns  of  above  100,000  inhabitants  .            . .          .  108 

All  towns  of  from  100,000  to  30,000       .            ...  96 

All  towns  of  from  30,000  to  20,000  inhabitants . .          .  92 

All  towns  of  from  20,000  to  10,000          .            ...  94 

All  towns  of  from  10,000  to  5,000           .            ...  73 

Chefs-lieux  d'arrondissenient  of  under  5,000  inhabitants  68 


Thus,  for  the 


lf-00. 

121 

112 

99 

95 

91 

74 


For  Prussia,  Laspeyres1  has  given  the  following  table,  which  is  based 
on  the  official  returns  for  the  period  1891-1895  : 


Large  towns 
Medium-sized  towns   . . 
Small  towns 
Towns  in  general 
Rural  districts  in  general 
Prussia  (average  for  whole) 


In  Austria,  the  cancer  mortality  for  the  towns  presents  a  similar 
gradation  (Kolb). 

For  the  towns  of  Bavaria,  the  cancer  death-rate  is  120,  and  for  the 
country  80. 

For  Saxony,  the  corresponding  figures  are,  for  the  towns  106,  and  for 
the  country  89  (Prinzing). 

In  Norway,  the  cancer  death-rate  for  the  towns,  in  1897,  was  100  ;  and 
for  the  rural  districts  80  (Geirsvold). 

Of  twenty-three  Dutch  towns  of  over  20,000  inhabitants  (1897-1900), 
fourteen  had  a  cancer  death-rate  above  the  average  for  the  whole  country 
(De  Bo  vis). 

These  data  prove  that  the  inhabitants  of  towns,  and  especially  of  the 
large  towns,  are  more  prone  to  cancer  than  those  of  the  small  towns  and"* 
of  the  rural  districts.  There  are,  however,  exceptions,  as  may  be  gathered 
from  study  of  the  previously  cited  data.  Moreover,  in  Switzerland, 
Denmark,  Sweden,  Norway,  Bavaria,  and  Baden,  all  of  which  have  very 
high  cancer  death-rates,  the  conditions  of  existence  are  predominantly 
rural ;  whereas  England,  Scotland,  and  Belgium,  whose  populations  are 
more  completely  urbanized  than  those  of  any  other  communities,  mani- 
fest only  moderate  proclivity  to  the  disease.  Among  the  towns  similar 
occurrences  are  noticeable — e.g.,  Geneva,  Rouen,  Lyons  etc.,  have  higher 
cancer  death-rates  than  Berlin,  Paris,  or  London  ;  the  cancer  death-rates 
of  Danzig  and  Keil  surpass  those  of  Berlin  ;  while  Florence  and  Ravenna 
have  a^greater  proclivity  to  cancer  than  Rome  etc. 

If  it  were  possible  to  correct  these  various  death-rates  for  diversities 
of  age  and  sex  distribution,  for  the  presence  of  hospitals  and  other  dis- 
turbing factors,  some  of  these  anomalies  might  then  be  less  conspicuous  ; 
but,  even  so,  the  main  indications  of  the  crude  data  would  not  be  changed. 
Thus,  as  Laspeyres  has  shown,  the  cancer  death-rates  of  men  from  sixty 
to  seventy  years  old,  in  the  large  towns  of  Prussia,  amounted  to  68 ; 
whereas  the  corresponding  figure  for  the  rural  districts  was  only  23-7, 
and  at  all  other  age  periods  similar  differences  were  noticeable.  These 
1  Central.-  Bl.  f.  ailg.  Qesundheitspftege,  1901,  S.  342. 


30  THE  NATURAL  HISTORY  OF  CANCER 

differences  cannot  be  explained  as  the  result  of  presumed  better  diagnosis 
by  the  urban  medical  practitioners,  as  I  shall  subsequently  have  occasion 
to  prove.  Therefore,  it  seems  clear  that,  in  modern  communities,  urban 
populations  are  generally  more  prone  to  malignant  disease  than  are  the 
rural  inhabitants.  In  Sweden,  however,  as  in  England,  it  has  been  noted 
that  the  cancer  death-rate  of  the  small  towns  surpasses  that  of  the  large 
ones ;  which,  with  other  similar  indications,  seems  to  show  that  the 
incidence  of  the  disease  is  determined  more  by  the  local  conditions  of 
existence,  than  by  urbanization  or  ruralization  per  se. 

Here,  however,  it  is  necessary  to  point  out  a  peculiar  feature  of 
cancer,  wherein  it  differs  from  nearly  all  contagious  diseases — viz.,  that 
its  incidence  never  shows  any  proportional  variability  with  mere  density 
of  population.  This  was  long  ago  shown  to  be  the  case  for  our  country 
by  Walshe,  C.  H.  Moore,  and  Haviland.  In  this  respect  cancer  differs 
markedly  from  tubercle. 

By  comparing  the  figures  showing  the  density  of  population  in 
European  communities,  with  those  indicating  the  corresponding  cancer 
death-rates,  very  striking  disparities  in  this  respect  are  at  once  revealed. 
Thus,  Belgium  and  England,  with  550  and  540  inhabitants  respectively 
to  a  square  mile,  are  the  most  densely  populated  communities  in  Europe  ; 
but  they  are  far  from  occupying  a  similarly  exalted  position  in  the  cancer 
list;  and,  although  nearly  equal  as  regards  density  of  population,  their 
proclivity  to  cancer  shows  no  corresponding  similarity.  Switzerland  and 
Denmark,  which  head  the  cancer  list,  have  only  a  medium  density  of 
population — viz.,  197  and  146  per  square  mile  respectively.  On  the 
other  hand,  Norway  and  S\veden,  the  most  sparsely  populated  countries 
in  Europe,  with  less  than  thirty  inhabitants  per  square  mile,  have  very 
high  cancer  death-rates. 

This  peculiarity  in  the  incidence  of  cancer  tells  against  contagion,  as 
the  causative  factor  of  variations  in  its  distribution  ;  and  points  rather  to 
diversities  in  the  conditions  of  existence,  and  especially  to  such  as  are 
independent  of  mere  density  of  population. 

General  Survey  of  the  Distribution  of  Cancer  in  Asia. 

All  available  indications  point  to  the  conclusion,  that  cancer  is  every- 
where much  less  prevalent  in  Asia  than  in  Europe. 

Nearly  all  the  old  writers  on  the  geographical  distribution  of  disease 
agree  in  stating,  that  cancer  is  more  prevalent  in  China  than  in  any  other 
Asiatic  community.  With  regard  to  recent  sources  of  information,  the 
mean  annual  death-rate  from  cancer  in  Hong-Kong  for  the  period  1895- 
1904,  was  4-45  per  100,000  inhabitants ;  1  while  that  for  England  and 
Wales,  during  about  the  same  period,  was  81. 

Of  2,981  Chinese  adults  admitted  in  the  Tang  Wah  Hospital  at  Hong- 
Kong  in  1900,2  8  had  malignant  tumours  ;  and  of  3,185  admitted  in 
1902,3  10  were  similarly  affected:  thus,  of  these  6,166  inmates,  18  had 
cancer,  or  1  in  342. 

1  Report  on  Cancer  in  British  Colonies,  1906. 
•  Report  of  the  Civil  Medical  Officer,  1900 

fiJ&iS  19°\  The   TanS   Wah   HosPital   w   a   kind   of   refuge 
f  the  Chinese  go  when  very  ill  or  moribund. 


GEOGRAPHICAL  DISTRIBUTION  AND  INCIDENCE         31 

Of  1,299  Asiatics  admitted  into  the  Government  Civil  Hospital  at 
Hong-Kong  in  1902,  11  had  cancer,  or  1  in  118. 

In  London  general  hospitals  the  proportion  of  inmates  affected  with 
cancer  has  lately  been  estimated  at  1  in  20. 

Of  the  1,305  deaths  of  Chinese  in  Hong-Kong  hospitals  during  the 
year  1902,  only  3  were  due  to  cancer,  or  1  in  435. 

A  few  years  ago  I  wrote  to  Dr.  Cantlie,  who  was  then  Government 
surgeon  at  Hong-Kong,  asking  him  for  information  on  this  subject.  He 
very  obligingly  replied  as  follows  :  "  I  do  not  think  I  have  been  without 
a  case  of  malignant  disease  under  my  care  ever  since  I  came  to  China 
six  years  ago."  Of  3,608  consecutive  Chinese  hospital  in-patients  under 
his  care,  114  had  malignant  disease,  or  1  in  31.  Of  Cantlie's  114  Chinese 
cancer  patients,  the  primary  seats  of  the  disease  were  as  follows  :  female 
breast,  38  ;  upper  jaw,  25  ;  lower  jaw,  14  ;  penis,  9  ;  uterus,  8  ;  parotid,  5  ; 
hip,  5  ;  tongue,  4  ;  lip,  3  ;  and  thigh,  3.  At  Dr.  Kerr's  hospital  in  Canton, 
during  the  year  1887,  30  cases  of  malignant  tumours  were  operated  on, 
including  11  amputations  of  the  female  breast.  Strange  to  relate,  Cantlie 
has  never  met  with  cancer  of  the  stomach  among  the  Chinese.  With 
regard  to  their  diet,  he  says  :  "  All  Chinamen  eat  fish  and  pork  at  morning 
and  evening  meals.  Fowls  and  ducks  are  always  on  the  table  of  all  but 
the  most  humble  of  the  coolie  class,  and  they  do  not  have  them  because 
they  cannot  afford  them.  I  hope  this  will  be  a  sufficient  answer  to  those 
who  maintain  that  Chinamen  live  on  rice.  It  is  not  nearly  so  true  as 
that  the  Scotch  live  on  porridge." 

In  the  Hong-Kong  district,  non-malignant  tumours  seem  to  be  even 
rarer  among  the  Chinese  than  the  malignant  ones,  for  of  6,166  hospital 
inmates,  only  8  were  thus  affected.  On  the  other  hand,  malarial  maladies 
are  very  common,  and  tubercle  is  prevalent,  according  to  Dr.  W.  Hunter. 

Dr.  J.  P.  Maxwell x  has  lately  published  some  valuable  information 
as  to  the  prevalence  of  malignant  tumours  in  the  province  of  Fokien, 
South  China,  which  is  situated  just  outside  the  tropical  zone. 

During  three  and  a  half  years,  11,000  patients  were  seen  at  the  Chang- 
poo  Hospital ;  and  of  these,  54  (males  42,  females  12)  were  subject  to 
these  maladies,  or  1  in  203.  Of  the  males,  24  suffered  from  cancer 
(oesophagus,  7  ;  pylorus,  2  ;  rodent  ulcer  of  the  face,  3  ;  penis,  2  ;  and 
1  each  as  follows  :  lip,  palate,  leg,  jaw,  tongue,  face,  scalp,  eyelid,  thyroid, 
and  groin) ;  and  18  from  sarcoma  (femur — periosteal,  3  ;  spindle-celled  of 
connective  tissue,  4  ;  neck,  5  ;  and  1  each  in  the  following  situations  : 
antrum,  upper  jaw,  lower  jaw,  naso-pharynx,  testis,  and  skin  of  back — 
melanotic).  Of  the  females,  7  had  cancer  (breast,  4  ;  oesophagus,  1  ;  and 
rodent  ulcer  of  the  face,  2) ;  and  5  had  sarcoma  (axilla,  1 ;  lymphadenoid, 
1  ;  upper  jaw,  1  ;  neck,  1  ;  and  lung,  1). 

The  population  furnishing  these  cases  lived  chiefly  on  rice,  only  a 
small  amount  of  animal  food  and  alcohol  being  consumed. 

According  to  Dr.  Elizabeth  Reifsnyder,2  of  Shanghai,  cancer  of  the 
uterus  and  breast  is  common  in  that  part  of  China,  and  ovarian  cystomata 
are  also  often  met  with. 

1  Journal  of  Tropical  Medicine,  September,  1904,  p.  270. 

2  American  Journal  of  Obstetrics,  etc.,  vol.  xxxi.,  1895,  p.  512. 


32  THE  NATURAL  HISTORY  OF  CANCER 

In  his  interesting  "  Notes  on  Surgical  Practice  among  the  Natives  of 
Shanghai,"  Dr.  E.  Henderson1  points  out  that  the  establishment  of  mission 
hospitals,  giving  gratuitous  treatment,  has  proved  that  cancerous  and 
sarcomatous  tumours  are  not  uncommon  among  the  natives  of  that 
vicinity.  Non-malignant  tumours  (lipoma,  etc.)  of  exceptionally  large 
size  are  also  fairly  often  seen,  owing  to  the  inabilityof  native  practitioners 
to  remove  them.  He  reports  cases  of  fibre-cystic  sarcoma  of  the  lower 
jaw  and  of  the  parotid  region,  under  his  own  observation.  Tuberculous, 
malarial,  and  syphilitic  affections  are  very  rife  The  staple  diet  com- 
prises rice  and  other  vegetable  products,  with  fish,  pork,  or  fowl  if  means 
permit.  Tea  is  the  usual  drink,  and  samshu,  a  native  spirit  made  from 
rice,  is  also  freely  taken,  but  hardly  ever  to  such  an  extent  as  to  cause 
drunkenness. 

According  to  a  recent  publication  by  Dr.  Brunet,2  cancer  is  com- 
paratively uncommon  in  those  parts  of  China  where  the  bulk  of  the 
people  live  on  an  almost  exclusively  vegetarian  diet,  being  too  poor  to 
purchase  any  of  the  various  flesh  foods  which  are  there  used  for  culinary 
purposes.  He  points  out  that  the  Chinese  altogether  eschew  milk  as 
food,  even  for  infants  ;  and  it  is  a  mistake  to  suppose  that  the  majority 
of  them  live  on  rice,  as  this  staple  can  only  be  afforded  by  families  whose 
means  are  above  the  average,  most  of  the  population  having  to  be 
satisfied  with  cheaper  grains,  such  as  millet. 

Dr.  Gray  3  reports  that  cases  of  cancer  of  the  mamma,  lip,  and  penis 
are  often  seen  at  the  mission  hospitals  in  North  China. 

At  the  hospital  for  Chinese  in  Tartar  City,  Pekin,  Dr.  Foulkes4 
found  that  cancer  was  fairly  common.  He  mentions  cases  of  epithelioma 
of  the  lower  lip  and  oesophagus,  and  spindle-celled  sarcoma  of  the  breast 
in  a  girl  aged  seventeen. 

In  the  United  States  (1900),5  the  48,565  Chinese  (mostly  adult  males) 
comprised  in  the  registration  area,  had  a  cancer  death-rate  of  49  per 
100,000  living,  or  about  1  in  40  of  the  total  mortality  from  all  causes. 
They  experienced  very  heavy  mortality  from  phthisis  and  pneumonia, 
but  the  deaths  from  malaria  were  very  few.  For  the  white  population, 
the  cancer  death-rate  for  all  ages  and  both  sexes  was  66  (males  50).  It 
would  seem,  therefore,  as  if  the  change  of  habitat  had  greatly  increased 
the  liability  of  the  Chinese  immigrants  to  malignant  disease.  A  similar 
occurrence  has  been  noted  in  Australia,  with  respect  to  the  Chinese  coolie 
immigrants  in  Victoria.6 

Malignant  tumours  are  believed  to  be  less  prevalent  in  Japan  than 
in  China  ;  however,  according  to  a  recent  estimate,  the  Japanese  cancer 
death-rate  is  placed  at  49  per  100,000  living,  but  on  what  evidence  this 
figure  rests  I  am  unable  to  say. 

It  accords  with  the  above-mentioned  belief,  that  the  Japanese  immi- 

1  Edinburgh  MedicalJournal,  vol.  xxii.,  1876,  pp.  405,  690 ;  and  vol.  xxiii.,  1877,  p.  118. 

2  fievue  d' Hygiene,  t.  xxvii.,  Nos.  2  and  3,  1905. 

3  Lancet,  1901. 

4  Indian  Medical  Gazette,  September,  1902,  p.  348. 

6  Twelfth  Census  Report  of  the  United  States  (1900). 

6  Lancet,  vol.  i.,  1904,  p.  424;  also  Australian  Medical  Gazette,  September  21,  1902. 
p.  169. 


GEOGRAPHICAL  DISTRIBUTION  AND  INCIDENCE          33 

grants  in  the  United  States  are  less  prone  to  these  diseases  than  the 
Chinese,  their  cancer  death-rate  in  1900,  being  24  per  100,000.  The 
Japanese  subsist  mainly  on  rice,  beans,  millet,  and  other  vegetable  pro- 
ductions, to  which  those  who  can  afford  it  add  fish,  eggs,  small  quantities 
of  meat  etc.  They  are  of  very  frugal  and  temperate  habits,  andr  arely 
indulge  in  alcoholic  drinks. 

In  Korea,  malignant  tumours  are  not  common,  but  most  of  the  chief 
local  varieties  have  been  met  with. 

Nothing  definite  is  known  as  to  the  incidence  of  these  maladies  in 
Northern  Asia  and  Siberia. 

In  Arabia,  Persia,  and  Asia  Minor,  cancer  is  reported  to  be  rare 
(Lombard)  ;  but  in  the  Caucasus  it  is  by  no  means  uncommon,  especially 
among  Russians  and  Armenians.  In  the  adjacent  province  of  Astrakhan 
cancer  is  moderately  prevalent,  and  tubercle  is  common  (Dallinger).  In 
Cyprus*  49  cases  of  malignant  and  100  of  non-malignant  tumours,  were 
met  with  among  about  30,000  hospital  and  dispensary  patients,  during 
1903. 

In  the  absence  of  statistical  reports  as  to  the  incidence  of  malignant 
tumours  and  other  diseases  among  the  immense  population  of  India, 
which  in  its  entirety  approximates  350,000,000,  all  estimates  must  be 
regarded  as  tentative  and  conjectural.  The  great  extent  of  the  country 
and  its  teeming  millions  make  it  very  difficult,  even  for  those  who  have 
been  long  resident  there  in  a  professional  capacity,  to  arrive  at  correct 
conclusions.  The  few  hospitals  and  dispensaries  in  India  draw  their 
patients  from  immense  multitudes  and  vast  areas,  so  that,  although 
many  cases  of  cancer  may  be  constantly  under  treatment,  the  propor- 
tionate prevalence  of  the  disease  in  the  general  population  may  be  much 
less  than  the  medical  officers  of  such  institutions  are  apt  to  believe.  After 
careful  study  of  all  available  sources  of  information,  it  appears  to  me 
clearly  indicated  that  malignant  tumours  are  very  much  less  prevalent, 
pro  rata,  in  India  than  in  Europe  ;  but  neither  the  Hindoos,  who  number 
over  200,000,000,  nor  the  Mohammedans,  who  number  over  60,000,000, 
nor  any  of  the  other  races  of  India,  can  claim  exemption. 

A  recently  issued  Government  Report,  based  on  the  percentage  of 
cancer  cases  to  the  total  number  of  all  diseases  treated  in  the  hospitals 
and  dispensaries  of  the  various  provinces,  gives  the  following  results  ; 
but,  for  the  reasons  above  stated,  the  incidence  of  the  disease  in  the 
general  population  is  certain  to  be  very  much  less  than  in  these  hospital 
and  dispensary  patients,  low  as  this  ratio  is  : 

Proportion  of  Cancer 

Provinces.  Cases  to  100  of  all 

other  Diseases. 

Punjab O'TOO 

Central  division    . .          . .          . .          . .          . .          . .     0'700 

Berar O'TOO 

Burmah 0'610 

Agra  and  Oudh O'OoO 

Bombay 0-050 

Bengal         0'025 

Madras 0'024 

Assam         O'OOS 

1  Colonial  Report,  1903. 


34  THE  NATURAL  HISTORY  OF  CANCER 

In  interpreting  these  figures,  it  is  necessary  to  remember  that  the 
patients  were  nearly  all  adults,  the  men  being  three  or  four  times  as 
numerous  as  the  women,  who  are  with  difficulty  persuaded  to  avail 
themselves  of  hospital  treatment. 

In  a  general  way,  it  may  be  said  that  all  the  varieties  of  malignant 
tumours  met  with  in  Europe  have  their  counterparts  in  India.  My 
statistics  show  that  in  English  hospital  patients  85-4  per  cent,  of  these 
growths  are  epithelial  cancer,  the  remaining  14-6  per  cent,  being  sarcomata. 
Most  Indian  statistics,  however,  reveal  a  much  greater  relative  proportion 
of  the  latter  ;  indeed,  the  data  from  some  districts  seem  to  show  that  sarco- 
mata are  nearly  as  prevalent  as  carcinomata.  A  remarkable  negative 
feature  of  the  Indian  Reports,  is  the  almost  complete  absence  from  them  of 
cases  of  malignant  disease  of  the  stomach  (pylorus) ;  and  an  equally  note- 
worthy positive  feature,  is  the  unusually  great  predominance  of  external 
cancers.1  Mammary,  uterine,  and  hepatic  cancers,  seem  to  be  relatively 
much  less  prevalent  in  India  than  in  England.  The  extraordinary  com- 
parative frequency  of  some  external  reputed  manifestations  of  the  disease 
in  India,  such  as  "  cancer  "  of  the  penis  and  cutaneous  system,  especially 
the  curious  "  Kangri-burn  cancer,"  is  so  unparalleled  in  European  experi- 
ence, and  these  lesions  seem  in  other  respects  so  different  from  epithelial 
cancer,  as  it  is  met  with  in  this  country ;  that  I  suspect  the  majority  of 
them  will  eventually  turn  out  to  be  pseudo-malignant  lesions  due  to 
microbic  infection  rather  than  true  cancer,  as  I  shall  subsequently  have 
occasion  to  point  out  more  in  detail. 

The  data  available  do  not  enable  us  to  determine  the  comparative  sex 
prevalence  of  the  disease,  owing  to  the  great  majority  of  hospital  patients 
being  males,  the  inhabitants  of  India  being  very  averse  to  their  women 
entering  hospitals. 

Some  valuable  information  as  to  the  incidence  of  malignant  disease 
in  the  Punjab  and  at  the  Mayo  Hospital,  in  Lahore  of  that  province,  has 
lately  been  published  by  Dr.  D.  W.  Sutherland.2  He  concludes  that 
cancerous  affections  are  not  at  all  common  in  this  part  of  India.  In  all 
the  Punjab  hospitals  and  dispensaries  for  the  years  1899-1903,  the 
yearly  average  of  patients  treated  for  malignant  tumours  was  266,  and 
the  proportion  of  these  tumours  to  the  total  cases  treated  for  all  diseases 
was  only  0-08  per  mille. 

At  the  Mayo  Hospital  in  Lahore,  during  the  decennium  1892-1903, 
43,412  in-patients  were  treated  ;  and  of  these,  792  had  some  form  of 
malignant  tumour  (carcinoma,  400  ;  sarcoma,  334),  or  1  in  55.  These 
patients  were  drawn  from  the  25,000,000  of  the  Punjab,  every  part  having 
contributed,  and  some  even  came  from  adjoining  States. 

In  the  population  of  the  Lahore  district,  Hindoos  and  Mohammedans 
are  about  equally  represented,  and  both  races  proved  to  be  about  equally 
liable  to  malignant  disease  ;  but  with  respect  to  carcinoma,  the  Hindoos 
were  eighty  cases  in  excess  of  the  Mohammedans,  owing  to  individuals  of 

°/  -f^  °TJ!£  ?tnCer  fr°m  ,India  analysed  by  the  Imperial  Cancer  Research  Fund 

kipLn^f    e     su  e  °f  the  body>  and  °niy  7e  internai  °rgans 

2  Arch.  Middlesex  Hosp.,  vol.  iii.,  1904,  p.  84. 


GEOGRAPHICAL  DISTRIBUTION  AND  INCIDENCE          35 

their  race  furnishing  seventy-two  cases  of  "  cancer  "  of  the  penis,  whereas 
there  was  not  a  single  case  of  this  local  variety  of  the  disease  among  the 
Mohammedans.     The  latter  practise  circumcision,  and  Sutherland  ascribes 
their  immunity  from  this  local  form  of  the  disease  to  this  custom.     The 
proportion  of  cases  of  carcinoma  of  the  penis  in  the  Hindoos,  is  so  enor- 
mously in  excess  of  what  is  met  with  in  Europe,  that  I  wonder  if  the  diag- 
nosis may  not  be  in  fault.     Is  it  quite  certain  that  in  most  of  these  cases, 
we  may  not  have  to  do  with  a  form  of  contagious  venereal  condyloma,yx 
to  which  the  well-known  libidinous  practices  of  the  Hindoos  render  them'  . 
specially  liable  ?  * 

Syphilis  and  malaria  are  of  great  frequency  among  the  populations 
whence  these  patients  came,  but  insanity  and  tubercle  are  rare.  With 
regard  to  their  diet,  both  races  are  mainly  vegetarian,  taking  only  a 
little  flesh  food  on  the  occasions  when  they  can  afford  it.  Alcoholic 
drinks  are  tabooed  by  the  Mohammedans,  but  the  Hindoos  indulge  freely 
in  them.  Nearly  half  of  the  total  patients  were  employed  in  cultivating 
the  soil,  much  smaller  numbers  were  shop-keepers,  general  labourers, 
beggars,  etc.  The  maximum  age  of  prevalence  for  carcinoma  was  from 
forty  to  fifty  (114  cases  out  of  395) — considerably  earlier  than  in  Eruope  ;)^ 
and  for  sarcoma,  of  350  patients,  79  were  from  thirty  to  forty  years  old, 
68  from  twenty  to  thirty,  58  from  forty  to  fifty,  and  44  from  ten  to  twenty 
years  old. 

With  regard  to  the  localization  of  the  disease,  the  most  striking  fact, 
next  to  the  frequency  of  "  cancer  "  of  the  penis  in  the  Hindoos,  is  the  "Xv 
complete  absence  of  malignant  disease  of  the  stomach,  of  which  not  a 
single  instance  is  recorded. 

The  chief  seats  of  carcinoma  in  396  cases  (males  270,  females  126) 
were  :  penis,  72  (all  Hindoos) ;  skin,  58  ;  breast,  50  ;  rectum,  30  ;  uterus, 
23  ;  liver,  23  ;  tongue,  20  ;  lip,  cheek,  mouth,  and  palate,  13  ;  bladder,  6  ; 
pharynx,  5  ;  larynx,  5  ;  anus,  5  ;  intestines,  3  ;  rodent  ulcer,  3  ;  pancreas, 
3  ;  oesophagus,  2  etc. 

The  chief  seats  of  sarcoma  in  334  cases  (males  255,  females  79)  were  : 
head  and  neck,  112  (jaws,  53  ;  face,  13  ;  orbit,  13  ;  nose,  10  ;  naso- 
pharynx, 9  etc.)  ;  lower  limbs,  59  (thigh,  17  ;  leg,  13  ;  knee,  9  ;  foot,  7 
etc.)  ;  upper  limbs,  24  (shoulder,  7  ;  arm,  6  ;  elbow,  4  ;  forearm,  4  ;  hand, 
3  etc.)  ;  trunk,  21  (abdomen,  7  ;  back,  7  etc.)  ;  various  organs  (testis,  8  ; 
parotid,  5  ;  ovary,  3  ;  tongue,  2  ;  breast,  1  etc.). 

In  the  above,  twenty-eight  cases  of  sarcoma  of  the  long  bones  are 
comprised. 

All  the  different  histological  varieties  of  carcinoma  and  sarcoma  were 
represented. 

In  Kashmir,  a  state  adjacent  to  the  Punjab,  with  a  population  of 
several  millions,  malignant  and  other  tumours  are,  according  to  Dr.  E.  F. 
Neve,2  not  particularly  rare  for  India. 

This  country  is  a  high-lying  valley,  surrounded  by  high  mountains, 
of  which  extensive  tracts  are  permanently  under  water,  while  large  areas 

1  Referring  to  cases  of    this   kind  in    Egypt,  where  cancer  is  phenomenally  rare, 
Dr.  Madden  says  :  "  Condylomata  flourish  with  truly  tropical  luxuriance." 

2  Indian  Medical  Gazette,  May,  1902,  p.  164. 

3—2 


36  THE  NATURAL  HISTORY  OF  CANCER 

are  liable  to  annual  floods.  During  the  summer  season  the  valley  is 
practically  an  alluvial  plain  covered  with  rice-fields  and  swamps,  yet 
malaria  is  rare.  Phthisis,  pleurisy,  and  pneumonia  are  also  rare,  but 
rheumatic  affections  are  prevalent.  The  people,  who  are  Hindoos,  live 
mainly  on  rice,  the  cultivation  of  which  is  their  staple  employment. 

During  the  decennium  1890-1899,  2,020  natives  with  tumours  were 
operated  on  at  the  Kashmir  mission  hospitals,  more  than  half  of  which 
were  malignant. 

Of  486  epithelial  cancers,  the  sites  were  as  follows:  "Kangri-burn 
cancer  "  (skin  of  abdomen,  thigh,  or  vicinity),  363  ;  female  breast,  29  ; 
leg,  21  ;  chest,  13  ;  eyelids,  6  ;  lip,  5  ;  head,  5  ;  face,  4  ;  foot,  3  ;  heel,  3 ; 
wrist,  3  ;  rectum,  3  ;  eyeball,  3  ;  ear,  3  ;  nose,  2  ;  neck,  2  ;  back,  2  ;  penis, 
2  etc.  Those  attacked  were  the  mature  and  elderly. 

As  compared  with  Sutherland's  statistics  for  the  adjacent  Punjab, 
some  extraordinary  diversities  in  localization  are  noticeable.  In  the 
first  place,  Neve  tells  us  that  more  than  three-fourths  of  all  his  epithelial 
cancers  were  of  the  peculiar  "  Kangri-burn  "  variety.  During  the  cold 
winter,  for  the  sake  of  warmth,  the  natives  carry  under  their  clothes,  in 
contact  with  the  lower  part  of  the  abdomen,  a  charcoal  fire-basket 
("  Kangri  ").  This  often  causes  burns  of  the  skin  of  the  abdomen,  thigh, 
etc.  As  the  result  of  constant  irritation  by  the  "  Kangri,"  the  resultant 
scars  often  become  converted  into  thickened,  raised  excrescences,  which 
eventually  ulcerate.  Foul,  excavated,  spreading  ulcers,  with  thick  raised 
edges,  thus  result.  The  adjacent  lymph-glands  become  similarly  affected, 
and  often  even  the  axillary  glands  as  well.  Death  is  commonly  caused 
by  septic  complications,  secondary  to  these  sloughing  ulcers,  which  some- 
times perforate  large  bloodvessels,  and  prove  fatal  in  this  way.  Excision 
of  the  disease  in  its  early  stage  is  absolutely  curative  ;  but  after  the  glands 
have  become  extensively  involved,  only  50  per  cent,  of  those  operated 
on  can  be  completely  cured.  The  important  question  arises  :  What  is 
the  real  nature  of  this  malady,  which  is  so  different  from  ordinary 
epithelial  cancer  in  its  main  features  ?  According  to  Neve,  it  is  cutaneous 
epithelial  cancer,  the  hard  fibrous  base  of  the  ulcers  being  infiltrated  and 
overlaid  by  masses  of  epithelial  new-formation,  containing  abundant 
"  nests,"  etc.  In  all  this,  it  seems  to  me,  we  scarcely  have  sufficient 
evidence  of  cancer,  especially  in  view  of  the  clinical  course  of  the  malady, 
its  curability  by  operation,  and  the  absence  of  metastases.  The  disease 
is  probably  more  akin  to  keloid  than  to  cancer ;  and,  like  the  former, 
it  is  probably  due  to  microbic  infection. 

If  this  peculiar  affection  is  removed  from  the  list  of  cancer,  it  will  be 
seen  that  the  latter  malady  is  exceptionally  rare  in  Kashmir. 

Another  noteworthy  feature  of  Neve's  statistics,  compared  with  those 
of  the  Punjab,  is  the  relative  rarity  of  cancer  of  the  penis.  The  uncir- 
cumcised  of  Kashmir  have  no  special  proclivity  to  this  local  variety  of 
the  disease,  which  supports  my  above-mentioned  contention  as  to  the 
non-cancerous  nature  of  most  of  the  Punjab  penile  cases. 

The  Kashmir  data  agree  with  those  from  the  Punjab,  in  indicating 
great  rarity  of  visceral  cancer,  specially  of  the  stomach,  liver  etc. 

With  regard  to  sarcoma,  of  154  cases,  23  were  unclassified  as    to 


GEOGRAPHICAL  DISTRIBUTION  AND  INCIDENCE         37 

locality  ;  of  the  others  the  sites  were  :  gum  (epulis),  21  ;  neck,  12  ; 
parotid.  12  ;  lower  jaw,  9  ;  upper  jaw,  7  ;  orbit,1  6  ;  leg,  6  ;  groin,  5  ; 
thigh,  5  ;  forearm,  5  ;  palate,  3  ;  base  of  skull,  3  ;  chest,  3  ;  back,  3  ; 
elbow,  3  ;  foot,  3  etc. 

The  most  noteworthy  feature  of  this  list  is  the  frequency  of  malignant 
"  epulis."  A  few  of  the  patients  were  young  children. 

Of  692  non-malignant  tumours,  the  distribution  was  as  follows  : 
papilloma,  120  ;  unclassified,  120  ;  polypi,  114  ;  lipoma,  106  ;  fibroma,  57  ; 
granuloma,  38  ;  horny,  29  ;  naevus,  27  ;  neuroma,  25  ;  keloid,  18  ;  chon- 
droma,  9  ;  osteoma,  6  ;  lymphoma,  5  ;  goitre,  4  ;  myxoma,  2  ;  molluscum 
fibrosum,  1  etc. 

Of  213  cysts,  the  following  subdivision  is  given  :  sebaceous,  124  ; 
ranula,  34  ;  ovarian,  15  ;  cystic  goitrej  15  ;  dermoid  (mostly  periorbital), 
12 ;  hydatid,  8  ;  serous,  7  ;  lactic,  2  ;  mesenteric,  2  ;  pancreatic,  1  ; 
parotid,  1  etc. 

It  is  remarked  of  the  sebaceous  cysts,  that  they  were   singularly  ^ 
common  in  certain  villages.     A  great  many  hydroceles  (298)  and  ganglions 
(44)  were  also  noted. 

In  Assam,  according  to  Dr.  Dalgetty,2  malignant  tumours  are  very 
rare.  His  experience  relates  to  Adampore,  in  South  Sylhet.  During  five 
years'  work  in  this  district,  among  a  labouring  population  of  12,000 
Hindoos — men,  women,  and  children — imported  from  various  parts  of 
India  to  work  in  the  tea-gardens,  he  met  with  only  eight  instances  of 
malignant  disease.  These  comprised  six  of  cancer — viz.,  four  males  (one, 
aged  thirty-five,  of  the  tongue  ;  one,  aged  forty-five,  of  lip  ;  one,  aged 
thirty-five,  of  mouth  ;  one,  aged  thirty,  of  penis)  and  two  females  (both 
of  the  cervix  uteri,  at  about  the  age  of  forty)  ;  and  two  of  sarcoma  (one, 
aged  thirty-five,  of  the  palmar  fascia  ;  one,  aged  thirty-five,  of  the  rib). 

Among  these  Hindoos,  2  cases  of  ovarian  cystoma,  1  of  uterine  myoma, 
and  1  of  lipoma  of  the  breast,  were  also  met  with. 

Of  15,000  resident  natives,  mostly  Mohammedans,  only  three  cases 
of  malignant  tumours  were  seen  during  the  same  period — viz.,  a  male, 
aged  fifty,  with  cancer  of  the  lip  ;  a  male,  aged  thirty-five,  with  sarcoma 
of  the  scalp  ;  a  male,  aged  thirty,  with  melanotic  sarcoma  of  the  eye. 
One  case  of  cystic  myoma  uteri  was  also  seen. 

Both  sexes  anoint  the  whole  body  with  cocoanut  oil ;  and  are  very 
free  from  warts  and  other  cutaneous  blemishes. 

The  district  is  highly  malarious,  and  it  may  be  safely  asserted  that 
every  one  of  the  above  patients  with  malignant  tumour  had  suffered  from 
malaria. 

Dr.  Drake,3  during  several  years'  practice  in  the  Thakurbarrie  district 
of  Assam,  when  he  was  in  charge  of  several  thousand  coolies  from  various 
parts  of  India,  as  well  as  of  the  natives  of  the  vicinity,  testifies  as  to  the 
rarity  of  malignant  tumours ;  for  he  never  saw  a  single  case. 

A  valuable  statistical  study  of  the  incidence  of  cancer  among  natives, 

1  In  a  recent  publication  Dr.  Xeve  mentions  the  eye  as  also  a  fairly  common  seat  of 
sarcoma  in  Kashmir.     British  Medical  Journal,  vol.  i.,  1906,  p.  1217. 

2  Journal  of  Tropical  Medicine,  April  15,  1902,  p.  122. 

3  Lancet,  vol.  ii.,  1904,  p.  1309. 


38  THE  NATURAL  HISTORY  OF  CANCER 

in  the  surgical  wards  of  the  Medical  College  Hospital  of  Calcutta,  during 
the  nine  years  1896-1904,  has  been  published  by  Dr.  Megaw.1  In  this 
series,  the  cases  of  cancer  occurring  in  the  medical  and  gynaecological 
wards  of  the  hospital  are  not  comprised.  11,446  surgical  hospital  patients 
furnished  343  cases  of  malignant  tumours  (1  in  33,  or  3  per  cent,  of  the 
total  admissions).  The  natives  of  India  are  very  loath  to  come  to 
hospitals  unless  afflicted  with  very  serious  disease — hence  "it  is  only 
natural  that  malignant  tumours  should  bulk  larger  in  Indian  statistics 
than  in  those  for  Europe."  The  local  conditions  in  the  two  cases  are, 
in  fact,  so  different  that  "  no  fair  comparison  as  to  the  relative  prevalence 
of  the  disease  in  India  and  Europe  can  be  based  on  the  above  data." 
Although  the  carcinomatous  form  of  the  disease  was  more  frequently 
met  with  than  the  sarcomatous,  yet  the  ratio  of  the  latter  to  the  former 
was  much  higher  than  in  Europe.  The  site-incidence  percentage  for 
carcinoma  was  as  follows  :  penis  and  scrotum,  20  ;  female  breast,  19-9  ; 
integument,  15-2  ;  ant  rum  and  palate,  9-9  ;  rectum,  1-7  ;  rodent  ulcer,  1-7  ; 
tonsil,  pharynx,  and  larynx,  1-7  ;  stomach,  0-9  etc.  For  sarcoma  the 
usual  seats  were  :  leg,  18-7  ;  neck,  18-7  ;  arm  and  axilla,  12-8  ;  jaws  and 
antrum,  10-1  ;  wall  of  trunk,  7-2  ;  testes,  5-4  ;  face,  5-3  ;  breast,  3-9  ; 
pharynx,  3-4 ;  abdominal  cavity,  3-4 ;  pelvis,  2-9  etc. 

The  Hindoos  were  found  to  be  more  frequently  affected  with  malignant 
disease  than  the  Mohammedans,  mainly  owing  to  their  greater  proclivity 
to  a  few  special  local  forms  of  the  disease — viz.,  to  "  cancer  "  of  the  penis, 
sixty-four  Hindoos  being  thus  affected,  and  only  two  Mohammedans  ;  to 
mammary  cancer,  fifty-seven  Hindoo  females  being  affected,  as  compared 
with  only  four  Mohammedans,  the  latter  having  great  reluctance  to 
hospital  treatment  for  their  women.  Hindoos  were  also  more  prone  to 
cancer  of  the  mouth,  cheek,  and  jaws  than  the  Mohammedans,  in  the 
proportion  of  49  to  1,  although  both  alike  indulged  in  betel-chewing,  to 
which  this  form  of  disease  has  often  been  ascribed. 

Dr.  McLeod,2  from  experience  in  Calcutta  hospitals,  concludes  that 
malignant  tumours  are  comparatively  common  among  the  natives  of 
Bengal,  both  in  hospital  and  private  practice  :  in  females  the  breast  being 
chiefly  affected,  and  in  males  the  cutaneous  system,  oral  cavity,  and 
especially  the  penis.  Of  254  tumours  operated  on  at  the  Medical  College 
Hospital  in  Calcutta  (1879-1883),  49  were  malignant  ;  and  of  333  tumours 
(1886-1890),  87  were  malignant.  Considering  that  the  Bengal  popula- 
tion, whence  these  hospital  cases  were  derived,  numbers  over  seventy 
millions,  the  proportion  of  cancer  cases  in  these  hospital  statistics  is  sur- 
prisingly small. 

According  to  Davidson,3  cancer  is  very  rare  in  Bombay,  only  0-1  per 
1,000  of  the  total  deaths  being  due  to  this  cause. 

Dr.  Niblock  *  has  tabulated  all  the  malignant  tumours  treated  at  the 
Madras  General  Hospital,  during  the  ten  years  1892-1901.  To  this 

*  Indian  Medical  Gazette,  May,  1905,  p.  103. 

"Operative  Surgery  in  Calcutta,"  1885,  p.   102;  also  "International  Text-Book 
of  Surgery,"  vol.  ii.,  1900,  p.  1206. 

'  "Geographical  Pathology,"  1892. 
4  Indian  Medical  Gazette,  April,  1902,  p.  161. 


GEOGRAPHICAL  DISTRIBUTION  AND  INCIDENCE         39 

hospital  patients  come  not  only  from  the  city  of  Madras,  which  has 
500,000  inhabitants  ;  but  also  from  all  parts  of  the  Madras  Presidency, 
which  comprises  a  population  of  over  40,000,000,  of  whom  three-quarters 
are  Hindoos,  and  the  rest  chiefly  Mohammedans.  During  the  decade 
under  consideration,  4,270  patients  were  treated  for  malignant  tumours, 
or  about  2-5  per  cent,  of  the  total  admissions.  From  these  figures  it  may 
be  concluded  that  malignant  disease  is  very  rare  in  Madras. 

Of  976  carcinomata  (males  746,  females  230),  the  localization  was  as 
follows  :  mouth,  411  (males  314,  females  97)  ;  penis,  200  (all  Hindoos)  ; 
tongue,  64  (males  58,  females  6)  ;  breast,  44  (all  Hindoos  except  one 
Mohammedan  female  ;  males  5,  females  38) ;  uterus,  46  (all  Hindoos)  ; 
jaws,  34  (males  30,  females  4)  ;  rectum,  33  (males  27,  females  6)  ; 
stomach,  21  (all  Hindoos  ;  males  14,  females  7)  ;  liver,  18  (males  15, 
females  3)  ;  skin  of  lower  limbs,  17  (males  11,  females  6)  ;  rodent  ulcer,  4 
(males  3,  females  1)  ;  and  vagina,  3. 

A  noteworthy  feature  about  the  above  data,  is  the  very  large  propor- 
tion of  cases  of  carcinoma  of  the  mouth  and  tongue  which  they  comprise, 
amounting  to  nearly  half  of  the  total.  Niblock  attributes  this  to  the 
prevailing  habit  of  "  betel  "-chewing.  Among  the  inmates  of  the  Lahore, 
Kashmir,  and  Assam  hospitals,  this  local  form  of  cancer  was  very  little  in 
evidence,  and  one  wonders  whether  "  betel  "-chewing  prevailed  among 
them.  Here,  again,  we  meet  with  a  very  large  proportion  of  cases  of 
"  cancer  "  of  the  penis,  all  among  Hindoos,  as  at  Lahore.  The  Hindoos 
of  the  great  cities  of  India  seem  to  have  special  proclivity  for  this  local 
variety  of  the  disease,  but  nothing  of  the  kind  is  noticeable  in  the  more 
rural  districts  of  Assam  and  Kashmir. 

Of  4,903  Hindoo  patients,  97  had  carcinoma,  or  1-98  per  cent.  ;  while 
of  339  Mohammedan  patients,  6  had  carcinoma,  or  1-76  per  cent. 

The  Eurasians  seemed  to  be  less  subject  to  cancer  than  any  other 
native  race  ;  and,  among  the  Hindoos,  several  of  the  patients  were 
Brahmins. 

Of  293  sarcomata  (males  217,  females  58,  children  12),  the  sites  of 
the  disease  were  as  follows  :  lower  limbs,  70  cases  (males  58,  females  11, 
children  2)  ;  neck,  35  (males  24,  females  9,  children  2)  ;  jaws,  33  (males  24, 
females  9)  ;  upper  limbs,  27  (males  25,  females  2)  ;  trunk,  17  (males  12, 
females  3,  children  2)  ;  face,  15  (males  9,  females  3,  children  3) ;  scalp 
and  skull,  13  (males  9,  females  4). 

Of  the  Hindoo  hospital  inmates,  0-67  per  cent,  had  sarcoma  ;  and  of 
the  Mohammedans,  0-49  per  cent. 

Among  the  natives  of  Ceylon,  malignant  tumours  are  very  rare,  the 
death-rate  from  this  cause  in  1897,  being  5  per  100,000  inhabitants,  or 
1  in  563  of  the  total  deaths.  Of  63,030  patients  treated  at  the  chief 
hospitals !  in  1900,  248  had  some  form  of  malignant  tumour,  or  1  in  254  ; 
and  of  6,501  deaths  of  the  hospital  patients,  27  were  due  to  malignant 
tumours,  or  1  in  241.  In  the  same  year,  256  cases  of  non-malignant 
tumours  were  under  hospital  treatment. 

According  to  Sir  A.  Perry,2  the  cancer  mortality  in  1903,  was  1  in 
every  16,820  persons  living,  or  about  6  per  100,000  inhabitants,  the  com- 

1  Colonial  Report,  Xo.  19,  1902.          2  Report  on  Cancer  in  British  Colonies,  1905. 


40  THE  NATURAL  HISTORY  OF  CANCER 

monest  seats  being  the  oral  cavity  and  penis.  The  island  is  highly 
malarious.  Tubercle  is  rare,  the  death-rate  from  this  cause  in  1903, 
being  91  per  100,000  living. 

In  Burmah  and  Siam,  malignant  tumours  are  perhaps  rather  more 
prevalent  than  in  India.  During  four  years'  residence  in  Siam,  Gowen1 
met  with  a  few  cases  of  carcinoma  and  sarcoma ;  but  Rasch  never  saw  a 
single  case  of  sarcoma  there.  In  Bangkok,  according  to  Nightingale,2 
although  malignant  tumours  are  seldom  seen  by  the  doctors,  they  are 
probably  less  rare  than  is  generally  believed. 

Among  the  Laos  people,  who  occupy  the  region  to  the  north  of  Siam, 
Hansen3  found  that  malignant  tumours  were  very  rare.  In  three  years' 
practice  he  only  met  with  a  single  case. 

In  the  hospitals  and  dispensaries  of  the  federated  Malay  States,4 
during  the  year  1903,  thirty-three  deaths  from  malignant  tumours  were 
recorded,  or  one  in  fifty-eight  of  all  the  fatal  cases  treated.  Altogether, 
during  the  year,  256  cases  of  malignant  and  297  of  non-malignant 
tumours  wrere  under  treatment.  Malarial  affections  are  very  prevalent ; 
and  there  is  a  considerable  tubercle  incidence,  especially  of  phthisis. 


General  Survey  of  the  Distribution  of  Cancer  in  Australasia  and  Oceania. 

Among  the  whites  of  Australia  and  New  Zealand,  cancer  is  much  more 
prevalent  than  in  any  other  part  of  Oceania,  and  also  than  in  Asia  ;  but 
its  incidence  is  much  less  than  in  England,  the  cancer  death-rate  per 
100,000  inhabitants  for  the  whole  of  Australia  being  57,  or  1  in  20  of  the 
total  deaths  (1900). 

All  the  local  authorities  state  that  malignant  growths  are  so  exceed- 
ing rare  as  to  be  almost  unknown,  among  the  aborigines  of  both  these 
countries.  According  to  G.  C.  Adams,5  the  Australian  aborigines  are 
"  practically  immune "  from  cancer.  In  Victoria,  of  seventy  deaths 
among  aborigines  registered  during  the  years  1894-1900,  only  one  was 
due  to  cancer.  These  natives  are,  however,  very  prone  to  tubercle,  and 
especially  to  phthisis.  The  Australian  aborigines  are  a  disappearing  race, 
who  now  form  only  an  insignificant  fraction  of  the  total  population,  for 
they  are  estimated  to  number  less  than  20,000.  During  ten  years'  experi- 
ence among  the  aborigines  of  Queensland,  Dr.  Roth  6  never  saw  a  single 
malignant  tumour.  For  a  young  country,  the  social  evolution  of  Australia 
has  of  late  pursued  a  peculiar  course.  Its  immense  territory  is  occupied 
by  a  mere  handful  of  people — some  3,750,000 — of  whom  the  great  bulk 
are  clotted  in  a  few  large  towns  on  the  coast  of  the  temperate  region, 
where  the  style  of  living  emulated  is  that  of  the  capital  cities  of  Europe. 
Under  the  influence  of  socialistic  ideas,  immigration  is  discouraged, 
although  the  declining  birth-rate  has  already  fallen  to  such  an  extent  as 
to  endanger  the  future  of  the  race.  Thus,  the  population  is  almost 

1  Janus,  1896,  1897,  and  1899. 

2  British  Medical  Journal,  vol.  ii.,  1902,  p.  835. 

3  Pacific  Medical  Journal,  January,  1902 

4  Colonial  Repoit  for  1903. 

5  Lancet,  vol.  i.,  1904,  p.  424. 

6  Report  on  Cancer  in  British  Colonies,  1905. 


GEOGRAPHICAL  DISTRIBUTION  AND  INCIDENCE         41 

stagnant ;  and  it  contains  an  unduly  large  proportion  of  adult  and  elderly 
persons.  Under  this  concatenation  of  artificial  circumstances,  and  with 
the  aid  of  the  lavish  expenditure  of  borrowed  millions,  a  high  standard 
of  individual  material  comfort  has  been  attained  in  this  "  worker's  para- 
dise." Owing  to  the  cheapness  of  meat  and  the  gluttonous  habits  of 
the  people,  the  amount  consumed  per  head  is  exceedingly  high.  Under 
these  circumstances,  the  tubercle  mortality  has  diminished,  while  the 
incidence  of  cancer  has  greatly  increased. 

A  curious  feature  with  regard  to  cancer  is  that  males  are  now  more 
prone  to  the  disease  than  females,  the  respective  death-rates  for  1900, 
being  59  and  55  ;  and  this  greater  proclivity  of  males  is  found  in  all  the 
different  states  of  the  Union. 

In  Australia,  as  in  Europe,  the  cancer  mortality  of  the  capital-city 
districts  is  much  higher  than  that  of  the  rural  districts,  the  rate  for  the 
former  being  81-3  (or  6-4  per  cent,  of  the  total  deaths  from  all  causes), 
as  against  44-7  for  the  latter  (or  3-9  per  cent,  of  the  total  mortality). 

Another  noteworthy  fact  about  the  Australian  statistics  is  that,  like 
those  of  the  United  States,  they  show  malignant  tumours  to  be  much  more 
prevalent  among  immigrants  than  among  those  born  in  the  country.1  X 

Thus,  for  all  Australia,  the  cancer  death-rate  in  1900,  was  57-3.  Of 
this  total,  the  British  and  foreign-born  immigrants  were  responsible  for 
40-2,  and  the  Australian-born  for  only  17-1.  If  only  persons  of  thirty-five 
years  of  age  and  upwards  are  included,  the  figure  for  the  total  cancer 
death-rate  will  then  be  195-3.  Of  this,  the  British  and  foreign-born 
account  for  137-1,  and  the  Australian-born  for  58-2.2  All  the  different 
races  of  immigrants  in  Australia,  experience  there  a  higher  cancer 
mortality  than  prevails  in  their  native  countries.  This  applies,  as  pre- 
viously mentioned,  even  to  the  Chinese.  Hence  it  may  be  concluded 
that  sudden  and  violent  changes  in  the  environment  are,  per  se,  potent 
factors  in  the  causation  of  cancer. 

The  cancer  death-rates  for  the  various  States  in  1900,  were  as  follows  : 
Victoria,  72  ;  South  Australia,  59  ;  New  South  Wales,  57  ;  Tasmania,  56  ; 
Queensland,  46  ;  West  Australia,  30. 

In  New  Zealand,  where  the  conditions  of  existence  and  of  social  evolu- 
tion somewhat  resemble  those  of  Australia,  the  leading  morbid  tendencies 
are  also  somewhat  similar.  Cancer  and  insanity  have  increased,  and  are 
increasing  ;  while  tubercle  is  declining.  The  people  are  prosperous,  with 
a  diminishing  birth-rate  ;  and  immense  quantities  of  flesh  food — chiefly 
beef  and  mutton — are  consumed.  "  Meat  for  breakfast,  lunch,  dinner, 
tea,  supper,  etc.,  just  like  the  porridge-pot  in  Scotland,"  as  Dr.  G.  Mac- 
donald,  of  Dunedin,  wrote  in  answer  to  my  letter  of  inquiry.  In  New 
Zealand,  as  in  Australia,  cancer  is  more  prevalent  among  males  than 
among  females.  The  cancer  death-rate  for  the  whole  country  in  1900, 
was  60. 

Among  the  inhabitants  of  the  South  Sea  Islands,  cancer  is  most  excep- 
tional. Dr.  Brennan,3  in  eleven  years'  experience,  never  saw  a  single 
case  among  natives  of  these  islands  labouring  in  Queensland. 

1  Immigrants  now  total  only  about  15  per  cent,  of  the  entire  population. 

2  Adams,  op.  cit.  3  Report  on  Cancer  in  British  Colonies,  1905. 


42  THE  NATURAL  HISTORY  OF  CANCER 

In  the  Fiji  Islands,1  malignant  tumours  are  very  exceptional,  since 
among  the  120,000  non-European  inhabitants,  of  whom  the  aborigines 
comprise  nearly  98,000,  the  rest  being  Indian  coolies,  Melanesians,  Poly- 
nesians, etc.,  only  two  deaths  occurred  from  this  cause  during  the  year 
1900  ;  and  there  were  also  only  two  deaths  from  non-malignant  tumours. 
In  1903,  five  Fijians  (two  being  half-castes)  died  of  malignant  disease — 
viz.,  one  of  carcinoma  (pylorus),  and  four  of  sarcoma  (orbit,  kidney, 
inferior  maxilla,  and  face). 

Sir  W.  MacGregor's  experience  2  is  to  the  same  effect.  He  says  :  "  I 
do  not  remember  ever  having  operated  on  a  Polynesian  or  Melanesian 
for  cancer,  though  I  have  had  to  do  so  sometimes  on  Europeans  in  Fiji." 
These  people  are  practically  vegetarians,  and  phthisis  was  not  known  in 
Fiji  until  it  was  brought  there  by  Europeans. 

In  New  Guinea,  malignant  tumours  are  equally  rare.  "  For  nine  and 
a  half  years,"  says  MacGregor,  "  I  never  saw  a  case  in  British  New  Guinea  ; 
but  at  the  end  of  that  time  there  occurred  an  example  of  sarcoma  of  the 
tibia  in  a  Papuan,  who  had  for  seven  or  eight  years  lived  practically  a 
European  life,  eating  tinned  Australian  meat  daily  "  etc.  Malarial  and 
venereal  affections  are  very  prevalent,  and  tuberculosis  as  well,  lupus 
exedens  also  is  common. 

In  Borneo,  cancer  is  quite  as  rare  as  in  New  Guinea.  Pagel,3  who 
practised  in  North  Bornea  for  ten  years,  never  saw  a  single  case  ;  and 
Nieuwenhuis  4  had  a  similar  experience. 

In  Java  and  Sumatra  it  is  just  the  same,  a  single  example  of  a  malig- 
nant tumour  in  a  native  being  esteemed  a  great  rarity  (Kohlbriigge,  Van 
der  Burg  etc.). 

In  the  Philippine  Islands  similar  conditions  prevail.  Thus,  of  631 
deaths  among  natives  at  Manila,5  during  the  month  of  February,  1903, 
in  which  the  causation  was  known,  there  was  not  a  single  instance  of 
cancer,  but  78  deaths  were  due  to  phthisis. 


General  Survey  of  the  Distribution  of  Cancer  in  Africa. 

No  part  of  the  world  is  believed  to  be  so  comparatively  immune  from 
cancerous  diseases  as  Africa,  and  this  applies  to  nearly  all  parts  of  the 
continent,  but  especially  to  its  northern  parts — Egypt,  Tunis,  Algeria  etc. 

A  few  years  ago,  desiring  to  ascertain  the  actual  incidence  of  the 
disease  in  Egypt,  I  wrote  to  Dr.  Engel,  of  Cairo,  who  is  in  charge  of  the 
Egyptian  vital  statistics,  and  he  kindly  supplied  me  with  the  following 
data  : 

Of  19,529  deaths  among  natives  of  Cairo  during  1891,  only  19  were 
due  to  cancer  (females  10,  males  9),  or  1  in  1,028.  In  England,  during 
the  same  year,  the  proportion  of  cancer  deaths  was  1  in  29. 

Of   12,950  patients  at  the  Kasr-el-Aini  Hospital  during  the  years 

1  Colonial  Report,  No.  19,  1902,  p.  141. 

2  Lancet,  vol.  ii.,  1900,  p.  1057. 

3  Deutsch.  med.  Woch.,  October  17,  1901. 

4  Janus,  1899. 

5  Journal  of  Tropical  Medicine,  July  1,  1904,  p.  208. 


GEOGRAPHICAL  DISTRIBUTION  AND  INCIDENCE         43 

1889-1891,  only  77  were  affected  with  cancer,  or  0-6  per  cent.  ;  whereas, 
in  London  general  hospitals  at  about  the  same  period,  I  have  ascertained 
that  the  proportion  of  cancer  patients  was  3-5  per  cent. 

From  these  data,  it  appears  that  the  reputation  of  Egypt  for  com- 
parative immunity  from  cancer  is  well  founded. 

In  this  Dr.  F.  C.  Madden,  of  Cairo,  concurs.  Thus  he  says  : l  "  The 
consensus  of  opinion  among  medical  men  in  Egypt  is,  that  cancer  is  never 
found  either  in  male  or  female,  among  the  black  races  of  that  country. 
These  include  the  Berberines  and  the  Sudanese,  who  are  all  Mussulmans, 
and  live  almost  entirely  upon  vegetarian  diet.  Cancer  is  fairly  common, 
however,  among  the  Arabs  and  Copts,  who  live  and  eat  somewhat  after 
the  manner  of  Europeans." 

Griesinger  states  that  he  never  met  with  a  single  case  of  cancer  of  the 
stomach,  during  many  years'  practice  in  Egypt. 

Insanity  is  phenomenally  rare  in  Egypt,  but  there  is  a  fair  amount 
of  tuberculous  disease,  including  phthisis  ;  while  malarial  and  venereal 
affections,  including  syphilis,  are  very  common,  "  condylomata  flourishing 
with  tropical  luxuriance  "  (Madden). 

Several  authors  have  called  attention  to  the  rarity  of  malignant 
tumours  among  the  natives  of  Algeria  (Legrain,  Kirmisson  etc.),  and 
have  ascribed  this  comparative  immunity  to  their  abstinence  from 
animal  food  and  intoxicating  drinks. 

The  official  statistics  for  Algeria2  relate  only  to  the  towns,  which 
comprise  for  the  most  part  a  large  European  element,  as  at  Algiers, 
where  the  cancer  death-rate  in  1895,  was  56  per  100,000  living  ;  but  at 
Oran,  where  there  are  but  few  Europeans,  the  cancer  death-rate  was 
only  1-3  ;  while  at  Biskra,  with  nearly  8,000  inhabitants,  at  Batna,  with 
over  6,000,  at  Mostaganem,  with  over  16,000  inhabitants,  not  a  single 
death  from  cancer  was  registered  ;  and  at  Guelma,  with  over  7,000  inhabi- 
tants, there  was  only  one  death  from  cancer. 

Many  travellers  have  commented  on  the  rarity  of  cancer  in  Tunisia  ; 
and,  according  to  Behold  and  Tiriant,  it  is  not  met  with  among  the 
aborigines.  • 

With  regard  to  the  incidence  of  cancerous  diseases  in  Morocco,  I  am 
indebted  to  the  late  Ernest  Hart  for  the  following  valuable  information. 
In  answer  to  my  letter  of  inquiry,  he  very  kindly  wrote  to  Dr.  Terry,  of 
Tangiers,  who  replied  as  follows  :  "  Cancers,  sarcomas  etc.,  do  not  seem 
to  be  very  prevalent.  At  any  rate,  the  number  of  cases  met  with,  as 
compared  with  other  diseases,  show  that  they  are  of  less  frequent  occur- 
rence than  in  England.  Among  the  inhabitants,  who  are  of  mixed  Arab 
and  native  blood,  I  have  seen  cancers  of  the  female  breast,  uterus,  and 
of  the  tongue,  as  well  as  sarcomatous  growths  in  various  parts  of  the 
body." 

In  Madeira  and  the  Canary  Islands  cancer  is  said  to  be  oftener  met 
with  than  in  North  Africa  (Behla)  ;  but  Dr.  J.  Goldschmidt3  has  found 
that  the  disease  is  decidedly  rare  in  the  former  island. 

1  British  Medical  Journal,  vol.  ii.,  1902,  p.  730. 

2  Statistique  sanitaire  des  villes  de  France  et  d' Algerie  pendant  I'annee  1895,  p.  114. 

3  Deutsche  med.  Woch.,  July  10,  1902. 


44  THE  NATURAL  HISTORY  OF  CANCER 

Among  the  natives  of  the  Sudan  seen  by  Dr.  A.  Balfour  1  at  Khartoum, 
instances  of  carcinoma  and  sarcoma  were  occasionally  met  with. 

During  his  visit  to  Somaliland  and  Erythrea  a  few  years  ago,  Fiaschi 2 
was  struck  with  the  remarkable  absence  of  malignant  tumours  among 
the  crowds  who  flocked  to  his  clinic,  although  tuberculous  and  syphilitic 
affections  were  common. 

We  have  no  recent  information  as  to  the  incidence  of  these  maladies 
in  Abyssinia,  but  by  the  older  writers  they  are  said  to  be  commoner  in 
this  country  than  in  any  other  part  of  Africa.  Dr.  C.  Singer,3  who  lately 
travelled  through  the  south-west  of  Abyssinia,  describes  goitre  and  Graves' 
disease  as  being  common  ;  and  in  a  Galla  he  saw  a  large  osteoma  of  the 
ribs,  but  he  makes  no  mention  of  having  seen  a  single  instance  of  cancer. 

On  the  West  Coast  malignant  tumours  are  very  .rare  among  the 
aborigines.  Malaria  is  exceedingly  prevalent,  but  tubercle  is  rare,  except 
among  natives  who  have  acquired  semi-civilized  habits.  The  records  of 
native  patients  treated  at  Bathurst,  in  Gambia,  for  many  years  contain 
not  a  single  entry  under  cancer  ;  and  Dr.  Forde,4  during  nine  years' 
practice  there,  never  saw  a  single  case. 

During  the  year  1903,  of  9,068  patients  (in  591,  out  8,477)  treated 
at  Government  hospitals  etc.,  not  a  single  instance  of  malignant  or  any 
other  tumour  was  met  with,  throughout  the  Gambia  colony. 

In  the  Gold  Coast  colonies  cancer  is  very  rare,  as  it  is  also  in  Ashanti. 
During  ten  years'  practice  in  the  latter  country,  Dr.  Henderson  5  never 
saw  a  single  case. 

According  to  Bornier,6  cancer  is  never  seen  among  the  Senegal  negroes. 
During  fourteen  years'  practice  at  Lagos,  Dr.  O.  Johnson  ?  saw  but  five 
instances  in  natives,  and  these  had  all  lived  for  many  years  a  semi- 
civilized  life,  eating  meat  etc.,  like  Europeans.  Plehn  met  with  only  a 
few  cases  of  sarcoma  among  the  natives  of  the  Cameroons.  In  British 
Nigeria,  during  1900,8  5,690  natives  were  treated  at  the  various  hospitals 
and  dispensaries,  but  not  a  single  death  from  malignant  -  tumour  is 
recorded. 

In  Uganda,  that  Central  African  community  where  the  indigenous 
civilization  attained  its  maximum,  malignant  tumours,  although  very 
much  less  common  than  among  Europeans,  are  said  to  be  by  no  means 
rare.  At  Dr.  Cook's  hospital  at  Mengo,9  cases  of  carcinoma  of  the  lip, 
oesophagus,  breast,  uterus,  intestine  etc.,  have  been  under  treatment ; 
as  well  as  cases  of  chondro-sarcoma  of  the  parotid,  sarcoma  of  the  jaws, 
melanosis  etc.  Uterine  myomata  and  ovarian  cystomata  are  also  fairly 
common,  as  well  as  various  other  non-malignant  tumours,  such  as  lipoma, 
fibroma,  enchondroma,  osteoma,  nsevus,  sebaceous  and  dermoid  cysts. 

Although  Uganda  has  a  cool  climate  for  Equatorial  Africa,  and  lies 

1  Journal  of  Tropical  Medicine,  April  15,  1904,  p.  118. 

British  Medical  Journal,  1897,  vol.  i.,  p.  687. 
3  Journal  of  Tropical  Medicine,  January  16,  1905,  p.  17. 

Report  on  Cancer  in  British  Colonies,  1905 

5  Ibid.,  1905. 

6  Path.  Compare,  etc.,  1889,  p.  254. 

7  Lancet,  vol.  ii.,  1900,  p.  1057. 

°  Colonial  Report,  No.  19,  1902,  p.  190. 

9  Journal  of  Tropical  Medicine,  June  1,  1901,  p.  173. 


GEOGRAPHICAL  DISTRIBUTION  AND  INCIDENCE          45 

high,  its  mean  elevation  being  4,000  feet  above  the  sea-level,  malaria  is 
exceedingly  prevalent,  constituting  nearly  25  per  cent,  of  all  the  cases 
treated.  Syphilis  also  is  rampant,  10-5  per  cent,  of  the  admissions  being 
for  this  disease  ;  while  tuberculous  maladies  account  only  for  4  per  cent. 
The  country  is  hilly,  and  many  of  the  people  are  affected  with  goitre  and 
albinism.  The  natives  are  clean,  intelligent,  and  "  splendidly  developed 
physically."  Their  staple  food  comprises  plantains,  bananas,  and  sweet 
potatoes,  while  banana  wine  is  extensively  consumed  ;  but  meat  can 
seldom  be  obtained.  In  other  parts  of  Central  Africa  cancer  is  decidedly 
very  rare.1  Thus,  Dr.  Scott,  of  the  Zomba  Mission,  who  has  been  in  the 
country  for  fifteen  years,  has  never  seen  a  single  case  ;  and  Dr.  Morris, 
formerly  of  the  Blantyre  Mission,  in  four  years'  work  saw  only  a  single 
case.  In  like  manner,  Dr.  Old,  during  four  years'  work  there,  met  with 
only  two  cases  of  malignant  disease,  while  Dr.  Hearsey's  2  testimony  is 
to  the  same  effect. 

Dr.  A.  R.  Sieveking,  now  of  Bristol,  who  practised  for  several  years 
among  the  natives  of  Masailand,  informs  me  that  he  never  saw  a  single 
example  of  malignant  tumour  among  them,  although  this  part  of  the 
country  was  well  stocked  with  big  game,  which  formed  an  important  part 
of  the  natives'  food  when  they  could  get  it. 

Among  the  natives  of  the  Nyassaland  plateau,  Dr.  Kellett-Smith 3 
found  that  all  kinds  of  malignant  tumours  were  so  rare  "as  to  be  prac- 
tically unknown."  Although  all  scars  tended  to  become  keloid,  yet 
these  keloids  never  took  on  malignant  properties.  Syphilis  seemed  to  be 
incapable  of  permanently  establishing  itself  among  the  natives.  Generally 
speaking,  in  British  Central  Africa  malignant  tumours  are  decidedly  rare. 

In  Mauritius  and  the  Seychelles  cancer  is  also  rare.  At  the  former 
place,  in  1903,  67  cases  of  cancer  were  met  with  among  21.356  hospital 
patients  ;  4  at  the  latter  place,  of  219  hospital  patients,  only  2  had  cancer 
(both  of  the  stomach).  In  the  mixed  population  of  St.  Helena  cancer  is 
not  uncommon. 

Livingstone5  speaks  of  cancer  as  being  absent  from  theBarotze  country, 
and  among  the  Bakwains,  although  the  latter  are  prone  to  fatty  and 
fibrous  tumours. 

The  natives  of  Mashonaland  and  Bechuanaland  are  said  to  be  equally 
exempt. 

In  Basutoland  malignant  tumours  are  rare.6  At  the  Leribe  Hospital, 
3,128  natives  were  treated  in  1900,  of  whom  4  had  malignant  and  25  non- 
malignant  tumours.  Of  4,684  patients  at  the  Maseru  Dispensary  in  the 
same  year,  2  had  cancer  and  44  various  non-malignant  tumours,  including 
6  cases  of  lipoma  and  3  dermoid  cysts.  Of  2,679  natives  treated  at  the 
Mafeking  Hospital,  6  had  cancer,  4  sarcoma,  and  22  various  non-malignant 
tumours  ;  and  at  Quthing,  of  1,242  patients,  2  had  cancer  and  7  non- 
malignant  tumours  (enchondroma,  3 ;  fibroma,  2 ;  lipoma,  2). 

1  Report  on  Cancer  in  British  Colonies,  1905. 

2  British  Medical  Journal,  1906,  vol.  ii.,  p.  1562. 

3  Liverpool  Med.-Chir.  Journal.  1901,  vol.  xxi.,  p.  46. 

4  Report  on  Cancer  in  British  Colonies,  1905. 

5  "  Missionary  Travels  in  South  Africa,"  etc.,  pp.  127,  504. 

6  Colonial  Report,  No.  19,  1902,  p.  25. 


46  THE  NATURAL  HISTORY  OF  CANCER 

Cancer  is  very  rare  among  the  natives  of  Natal,1  especially  among  those 
of  Bantu  origin,  for  out  of  a  population  of  86,000,  with  a  general  death- 
rate  of  19  per  1,000,  only  one  death  was  ascribed  to  this  cause  in  1903. 

An  example  of  a  large  sarcoma  of  the  lumbo-sacral  region  in  a  Zulu, 
aged  thirty,  has  lately  been  described  by  Dr.  H.  Goodman,  of  Johannes- 
burg.2 

According  to  Hawes,3  cancer  is  very  rare  among  the  Hottentots.  He 
has,  however,  met  with  three  instances  in  natives  of  this  race,  one  of 
whom  had  lived  for  many  years  as  a  servant  in  an  English  family. 

Among  the  Boers  and  Europeans  living  in  South  Africa,  who  are 
large  flesh-eaters,  malignant  tumours  are  common  ;  but  among  the 
natives,  who  are  mainly  vegetarians,  these  tumours  are  so  rare  as  to  be 
almost  unknown. 


General  Survey  of  the  Distribution  of  Cancer  in  America. 

Owing  to  the  fact  that  compulsory  death  registration  in  the  United 
States  is  confined  to  a  limited  area  (comprising  a  population  of  about 
29,000,000) ;  while  for  the  rest  of  the  country  (comprising  a  population 
of  over  47,000,000),  the  statisticians  have  to  depend  for  their  information 
on  the  data  supplied  by  the  "  enumerators,"  who — as  we  are  told  in  the 
introduction  of  the  official  report 4 — often  fail  to  make  inquiry  as  to  the 
cause  of  death,  or,  indeed,  to  make  any  return  of  deaths  at  all,  the  official 
reports  compare  unfavourably,  so  far  as  accuracy  and  reliability  are 
concerned,  with  corresponding  European  publications. 

In  consequence  of  this  unsatisfactory  state  of  affairs,  we  have  two 
estimates  as  to  the  incidence  of  cancer  in  the  United  States,  the  one 
based  on  the  returns  for  the  whole  country,  the  other  on  the  more  reliable 
data  for  the  "  registration  area." 

According  to  the  former,  the  cancer  5  death-rate  in  1900,  was  43  per 
100,000  living,  being  1  in  2,309  of  the  total  population,  or  1  in  31  of  the 
total  deaths. 

According  to  the  latter,  the  cancer  death-rate 6  was  60  for  the  same 
year,  being  1  in  1,665  of  the  total  population,  or  1  in  29  of  the  total 
deaths. 

Of  these  two  estimates,  the  latter  is  the  more  reliable  ;  but  my  im- 
pression is  that  both  of  them  understate  the  incidence  of  the  disease, 
which  is,  I  expect,  but  little  less  in  the  United  States  than  in  Europe. 

In  the  "  registration  area,"  the  death-rates  from  the  disease  in  the 
various  states  were  as  follows  :  Maine,  83 ;  Vermont,  81 ;  Columbia,  71 ; 
New  Hampshire,  66  ;  Massachusetts,  66  ;  Rhode  Island,  62  ;  New  York, 
61  ;  Connecticut,  61  ;  Michigan,  58  ;  and  New  Jersey,  50. 

In  the  United  States,  as  in  Europe,  Australia  etc.,  the  cancer  mortality 
is  increasing. 

For  the  chief  towns  the  rates  were  as  follows:  San  Francisco,  112 

1  Report  of  Medical  Officer  of  Health  for  Natal  for  the  year  1903. 

2  Transvaal  Medical  Journal,  May,  1906,  p.  319. 

3  Bartholomew's  Hospital  Reports,  vol.  xli.,  1906,  p.  161. 

4  Twelfth  Census  Report  of  the  United  States,  1900,  vol.  iii.,  part  i. 

5  Comprises  cancer  and  tumour.  6  Without  tumour. 


GEOGRAPHICAL  DISTRIBUTION  AND  INCIDENCE          47 

(1900) ;  Boston,  76  (1898) ;  Philadelphia,  73  (1900) ;  Baltimore,  69  (1904) ; 
New  York,  64  (1900) ;  New  Orleans,  64  (1898) ;  Chicago,  63  (1900) ;  Buffalo, 
53  (1899)  etc. 

The  returns  indicate  greater  prevalence  of  the  disease  in  rural  (death- 
rate  71),  than  in  urban  districts  (death-rate  65)  ;  but,  for  the  reasons 
above  mentioned,  too  much  importance  should  not  be  attached  to  these 
estimates. 

Another  source  of  fallacy  in  the  United  States  vital  statistics  is  that 
"  cancer  and  tumour  "  are  "  considered  together,  as  it  is  found  impossible 
accurately  to  distinguish  them,  as  they  are  commonly  reported."  * 

In  all  parts  of  British  North  America  cancer  is  fairly  common  among 
the  whites,  probably  about  as  common  as  in  the  United  States,  but  I 
have  been  unable  to  meet  with  any  satisfactory  recent  statistics.  Among 
the  aborigines  of  Canada,  Landry  2  (1861)  found  that  cancer  was  exceed- 
ingly rare,  and  it  is  still  very  infrequent. 

Of  3,275  necropsies  at  the  chief  Montreal  hospitals  (up  to  1904),  275, 
or  1  in  11-9,  were  for  cancer.  This  nearly  corresponds  with  the  ratio  in 
German  hospitals,  which  has  been  estimated  at  1  in  12  ;  and  the  Guy's 
Hospital  records  show,  that  1  in  8  of  all  necropsies  there  are  for  cancer. 

In  the  province  of  Ontario  there  were  1,055  deaths  from  malignant 
tumours,  in  1900. 

For  some  of  the  chief  towns,  the  cancer  death-rates  per  100,000  living 
in  1891,  were  as  follows  :  Halifax,  54  ;  Quebec,  42 ;  Montreal,  39  ;  Toronto, 
36  ;  and  St.  John,  15.  For  Victoria  (British  Columbia)  the  rate  was  110 
in  1896. 

In  Mexico  cancer  is  fairly  common  among  those  of  European  descent, 
who  live  in  the  high,  cool  regions,  and  even  the  semi-civilized  natives  and 
half-castes  are  affected  ;  3  but,  according  to  Jourdanet,  it  is  almost  un- 
known in  the  low-lying  hot  regions. 

In  the  Central  American  communities  the  disease  is  rare,  the  Guate- 
malan cancer  death-rate  for  1894,  being  only  4 ;  and  in  British  Honduras 
the  malady  is  equally  rare. 

In  the  Bermudas*  malignant  tumours  are  met  with  among  those  of 
white,  as  well  as  those  of  coloured  descent ;  thus,  of  423  deaths  in  1900, 
13  were  due  to  this  cause,  or  1  in  33. 

Of  145  deaths  among  whites,  8  (males  2,  females  6)  were  due  to  cancer, 
or  1  in  18  ;  of  278  deaths  among  the  coloured,  5  (males  1,  females  4)  were 
due  to  this  disease,  or  1  in  56. 

In  the  Bahamas,5  with  a  population  of  54,709  (mostly  coloured),  and 
a  general  mortality  of  1,231,  during  the  year  1900,  there  was  only  one 
death  from  cancer. 

Generally  speaking,  cancer  is  decidedly  rare  in  the  West  Indies,  but 
more  than  half  a  century  ago  L.  Young  had  noted  occasional  examples 
of  it.  Thus  he  says  : 6  "  Among  West  Indian  negresses  malignant  disease 
of  the  uterus  and  mamma  is  of  very  rare  occurrence,  and  even  those 

Twelfth  Census  Report  of  United  States,  1900,  vol.  iii.,  part  i.,  p.  clxixi. 

Bull,  de  la  Soc.  d'Anthropologie,  t.  ii.,  p.  16. 

Rodman,  "  International  Text-Book  of  Surgery."  vol.  ii.,  1900.  p.  731. 

Colonial  Report,  No.  19,  1902.  6  Ibid.,  p.  20. 

Cited  by  Astley  Cooper  in  his  "  Anatomy  of  the  Breast,"  etc.,  1840. 


48  THE  NATURAL  HISTORY  OF  CANCER 

cases  which  I  have  witnessed  in  this  class  of  people  have  been  among  the 
better  orders  of  them,  whose  habits  of  living  have  been  assimilated  to 
those  of  Europeans." 

In  Jamaica  the  death-rate  from  this  cause  in  1888,  was  nearly  12  per 
100,000  living,  which  in  1905  had  increased  to  19.  The  phthisis  death- 
rate  for  the  island  amounted  to  155  in  1903,  and  the  average  for  1895- 
1904  has  been  160. 

Of  1,317  deaths  in  the  hospitals  of  Trinidad  and  Tobago  1  during  1900, 
13  were  due  to  malignant  tumours,  or  about  1  in  102.  The  localities 
affected  were  the  female  genitalia  in  5  cases,  the  liver  in  3  cases,  and  1 
each  of  the  mamma,  stomach,  and  larynx.  Fifty-five  cases  of  non- 
malignant  tumours  were  also  treated  at  these  hospitals,  including  23 
uterine  myomata  and  2  ovarian  cysts. 

In  the  various  hospitals  of  Grenada,2  in  1900,  490  patients  were  under 
treatment,  of  whom  8  had  malignant  tumours,  or  1  in  62. 

At  St.  Lucia,3  of  2,810  hospital  patients,  with  159  deaths,  in  1900, 
5  were  due  to  cancer,  or  1  in  32  of  the  deaths.  Twenty- two  patients  were 
treated  for  non-malignant  tumours  during  the  same  year. 

Of  30,856  natives  of  St.  Kitts,*  899  died  during  1900,  malignant 
tumours  being  the  cause  of  death  in  4.  Thus,  the  cancer  death-rate  per 
100,000  living  was  nearly  13,  or  1  in  225  of  the  total  deaths. 

Among  the  2,463  Europeans,  there  was  not  a  single  death  from  this 
cause  during  the  year. 

At  Nevis,5  with  a  population  of  14,520  natives,  of  whom  294  died 
during  the  year,  there  was  not  a  single  death  from  cancer. 

In  Anguilla,6  with  a  native  population  of  4,424  and  55  deaths,  only 
one  death  from  cancer  occurred  during  the  year,  the  rectum  being  the 
part  attacked.  With  regard  to  this  case,  the  medical  officer  says  in  his 
report  :  "A  few  deaths  from  cancer  are  recorded  as  having  occurred 
among  the  black  population  prior  to  my  arrival  in  the  island  ;  but, 
during  my  three  years'  residence  here,  I  have  only  seen  this  one  case  of 
cancer  among  the  blacks.  The  whites  are,  however,  fairly  often  attacked, 
especially  with  ulcerated  forms  of  cutaneous  cancer."  Thus,  of  32  deaths 
among  whites  during  the  period  1892-1900,  5  were  due  to  cancer  ;  where- 
as, of  479  deaths  among  the  blacks  during  the  same  period,  only  2  were 
due  to  this  cause.  Phthisis  and  malaria  are  common  in  the  island. 

In  the  tropical  parts  of  South  America  cancer  is  decidedly  rare  among 
the  natives. 

In  British  Guiana?  of  148,221  patients  treated  at  the  public  hospitals 
during  the  year  1903-1904,  only  105  had  malignant  tumours  ;  and  there 
were  93  instances  of  non-malignant  tumours.  Of  1,556  deaths  in  these 
hospitals  during  the  same  year,  27  were  due  to  malignant  disease.  Malaria 
and  tubercle  are  very  prevalent,  the  latter  malady  causing  13-9  per  cent, 
of  all  deaths. 

Spitzly,8  during  a  sojourn  of  eight  years  in  the  Surinam   district   of 

1  Colonial  Report,  No.  19,  1902.  2  Ibid 

I  Ibid.  *  Ibid.  s  Ibid  6  Ibid] 

7  Report  of  the  Medical  Department  of  British  Guiana,  1903-1904. 

8  British  MedicalJournal,  vol.  i.,  1902,  p.  16. 


GEOGRAPHICAL  DISTRIBUTION  AND  INCIDENCE  ;       49 

Dutch  Guiana,  found  that  the  various  forms  of  malignant  tumours  were 
not  very  common  there.  He  met  with  the  following  cases  :  cancer  of 
the  tongue  in  an  escaped  Cabyle  convict,  malignant  disease  of  the  glands 
of  the  neck  in  a  Guiana-born  Jew  of  fifty,  melanotic  sarcoma  of  the 
external  auditory  meatus  in  a  coloured  man  from  Niekerie,  cancer  of 
the  tongue  in  a  Chinaman,  several  cases  of  mammary  cancer  in  Creole 
women,  malignant  disease  of  the  bladder  in  a  middle-aged  coloured  native 
of  Paramaribo  who  was  a  prison  warder,  several  cases  of  cancer  of  the 
lip  and  penis  in  coloured  people  who  had  always  lived  in  Surinam,  etc. 
Malaria  is  very  prevalent  in  Dutch  as  in  British  Guiana. 

Cancer  is  rare  in  Brazil,  especially  in  the  Equatorial  regions,  the  death- 
rate  from  this  cause  for  1903,  being  only  4  per  100,000  living  (Sodre).i 
The  uterus  is  the  part  oftenest  affected,  gastro-intestinal  localizations 
being  comparatively  rare.  The  maximum  of  frequency  is  attained  in 
the  province  of  Rio  Grande  do  Sul.  For  Rio  di  Janeiro,  with  its  popula- 
tion of  850,000,  the  cancer  death-rate  was  about  26  per  100,000  living  in 
1904,  the  tubercle  mortality  being  287,  that  for  malaria  70,  and  the 
general  death-rate  from  all  causes  2,050. 

In  Uruguay  cancer  is  comparatively  common,  the  death-rate  from 
this  cause  in  1897,  being  47,  or  3-28  per  cent,  of  the  total  deaths,  and 
tubercle  is  prevalent. 

In  Argentina  cancer  is  also  fairly  common,  especially  in  Buenos  Aires, 
where  the  rate  in  1900,  was  91.  In  the  province  of  Tucuman,  the  cancer 
death-rate  for  1898,  was  only  10. 

1  Brazil  Med.  (Rio  di  Janeiro),  1904,  vol.  xviii.,  p.  229. 


CHAPTER  III 

THE  INCREASE  OF  CANCER,  AND  ITS  CONCOMITANTS 
Preliminary  Review. 

IN  the  course  of  organic  evolution  some  types  of  disease,  like  species, 
have  diminished  and  become  extinct,  while  others  have  increased  and 
become  more  prevalent.  In  comparatively  recent  times  typhus  fever, 
leprosy,  malaria,  scurvy,  plague,  and  dysentery  have  almost  or  quite 
disappeared  from  our  country  ;  small-pox  and  other  zymotic  diseases 
have  greatly  diminished  ;  while  phthisis  and  tuberculous  affections  are 
decidedly  on  the  wane. 

On  the  other  hand,  a  small  group  of  maladies,  of  which  cancer  is  the 
chief,  has  steadily  increased ;  and  this  in  spite  of  progressive  diminution 
in  the  general  death-rate,  with  other  signs  of  material  prosperity.  Of 
the  other  members  of  this  group,  insanity,  suicide,  alcoholism,  diabetes, 
and  diseases  of  the  circulatory  system,  are  the  chief ;  while  to  these  'may 
be  added  premature  births  and  congenital  deformities. 

In  all  modern  communities,  where  the  occidental  type  of  civilization 
prevails — of  which  the  chief  characteristics  are  industrialism  and  urbaniza- 
tion, with  great  increase  and  widespread  diffusion  of  material  prosperity 
— a  similar  tendency  is  noticeable,  especially  as  regards  cancer,  the  inci- 
dence of  this  malady  having  doubled  in  frequency  in  periods  of  from 
twenty  to  thirty  years,  the  annual  increment  of  increase  averaging  from 
3  to  5  per  cent. 

This  tendency  seems  to  be  of  comparatively  recent  origin.  At  any 
rate,  cancer  is  a  disease  of  great  antiquity,  which  is  known  to  have 
existed  from  the  most  remote  times  of  which  we  have  any  record.  The 
"  Papyrus  Ebers,"  which  is  believed  to  have  been  written  about  1550  B.C., 
contains  a  short  section  on  malignant  and  other  tumours,  from  which  it 
may  be  inferred  that  the  cardinal  features  of  these  maladies  were  then 
well  recognized.  In  the  works  of  Hippocrates,  who  is  believed  to  have 
flourished  during  the  latter  part  of  the  fifth  century  B.C.,  malignant  and 
other  tumours  are  referred  to  ;  but,  in  the  somewhat  detailed  enumeration 
of  the  various  maladies  prone  to  occur  at  the  different  periods  of  life, 
which  is  embodied  in  the  "  Aphorisms,"  no  mention  is  made  of  cancer. 
From  this  omission,  and  from  the  comparative  paucity  of  the  references 
to  cancer  in  the  Hippocratic  writings,  I  conclude  this  affection  must  then 
have  been  comparatively  rare. 

We  have  singularly  little  trustworthy  information  as  to  the  pre- 
valence of  cancer  in  this  country  during  the  Middle  Ages  and  at  earlier 

50 


THE  INCREASE  OF  CANCER,  AND  ITS  CONCOMITANTS      51 

periods  ;  but  from  such  indications  as  are  available,  it  seems  likely  that 
the  malady  then  was  of  much  less  frequent  occurrence  than  in  modern 
times.  The  exceptionally  well-kept  registers  of  Market  Deeping  (Lin- 
colnshire), during  the  years  1711  to  1723,  in  a  total  of  387  deaths,  show 
only  two  from  cancer  (one  male  and  one  female).1 

A  unique  statistical  study  of  cancer  incidence,  during  the  whole  of 
the  nineteenth  century,  has  been  made  by  Ekblom  2  for  the  small  Swedish 
town  of  Fellingsbro.  Taking  the  averages  for  the  first  and  last  decennial 
periods  of  the  century,  he  found  that  the  cancer  death-rate  had  increased 
from  2-1  per  100,000  living  in  the  former  period,  to  118  in  the  latter. 

The  data  derived  from  the  long  experience  of  the  Scottish  Widows' 
Life  Assurance  Fund,3  are  also  of  value  in  this  connexion.  Thus,  the 
proportion  of  deaths  due  to  cancer,  to  the  total  mortality  among  the 
males  assured  since  1815,  has  shown  the  following  increases  : 

Per  Cent. 
1815  to  1844  . .     .    .      .  0'93 


1845 
1859 

1867 
1874 
1881 
1888 


1858 
1866 
1873 
1880 
1887 
1894 


T79 
3-00 
4-56 
4'93 
5'44 
6'88 


The  experience  of  the  chief  German  Life  Assurance  Company,  as 
lately  reported  by  Juliusberger,4  is  to  the  same  effect.  Thus,  the  cancer 
mortality  among  males,  in  the  period  1885-1889,  amounted  to  3-7  per 
cent,  of  the  total  deaths,  and  among  females  to  114  per  cent.  ;  whereas, 
for  the  period  1889-1895,  the  corresponding  ratios  were  11-4  for  men 
and  12-9  for  women. 

England  and  Wales. 

Statistical  Summary. 

In  this  country  the  civil  registration  of  births,  deaths,  and  marriages 
came  into  operation  in  1837  ;  and  the  first  annual  report  of  the  Registrar- 
General  (for  the  year  ending  June,  1838)  was  published  in  1839,  the  cancer 
death-rate  then  being  166  per  million  living.  In  the  sixty-eighth  of  these 
reports — for  1905 — this  rate  had  increased  to  885,  or  more  than  fivefold. 

In  the  very  earliest  years  of  registration,  before  the  enumerating 
machinery  had  been  perfected,  the  data  elicited  may  have  left  something 
to  be  desired.  We  will  therefore  commence  our  study  with  the  year 
1840,  when  the  national  statistics,  under  the  able  direction  of  William 
Farr,  had  already  acquired  well-deserved  reputation  for  reliability. 

In  that  year  2,786  persons  died  of  malignant  disease  in  England  and 
Wales,  the  proportion  being  1  in  5,646  of  the  total  population,  1  in  129 
of  the  total  mortality,  or  177  per  million  living. 

In  1905  the  deaths  due  to  this  cause  numbered  30,221,  being  1  in 
1,131  of  the  total  population,  1  in  17  of  the  total  mortality,  or  885  per 
million  living. 

1  British  Medical  Journal,  vol.  i.,  1896,  p.  915  (Newman). 

2  Htjgeia,  January,  1902. 

3  Causes  of  death  among  the  assured  in  the  Scottish  Widows'  Fund  (C.  Muirhead), 
1902,  Edin.  Appendix.  *  Zeite.  f.  Krebsforschung,  1905. 

4—2 


52  THE  NATURAL  HISTORY  OF  CANCER 

In  this  respect,  the  position  occupied  by  cancer  is  unique,  for  no 
other  malady  can  show  such  a  great  increase.  Thus,  whatever  the 
etiological  factors  of  cancer  may  be,  it  is  evident  that  they  are  not  con- 
stant in  action ;  and,  if  capable  of  exacerbation  in  some  circumstances, 
they  may  be  amenable  to  diminution  in  others.  In  this  direction,  it 
seems  to  me,  we  may  reasonably  hope  to  discover  indications  that  will 
show  us  how  to  check  the  increase  of  the  malady,  and  even  enable  us 
eventually  to  greatly  reduce  its  mortality. 

I  believe  that  the  tendency  to  cancer  may  be  increased  by  unsuitable 
modes  of  living,  and  vice  versa-  We  must  therefore  seek  out  those 
conditions  which  favour  its  development ;  and,  by  avoiding  them,  we  shall 
then  be  able  to  effect  our  object.  In  my  opinion,  it  is  only  by  progress 
along  such  lines,  that  the  prevention  of  cancer  is  ever  likely  to  be  effected. 

In  further  illustration  of  this  subject,  I  have  compiled  the  following 
table  (see  p.  53),  which  shows  the  increments  of  increase  during  the  long 
succession  of  years. 

The  Reality  of  the  Increase. 

With  these  figures  before  us,  and  all  that  they  imply,  there  can  be  no 
doubt  as  to  the  reality  of  the  increase  in  the  cancer  mortality.  Yet  this 
has  been  called  in  question.  The  earliest  objectors  ascribed  the  registered 
augmentation  to  mere  increase  of  population ;  but  the  futility  of  this  is 
demonstrated  by  the  fact  that,  while  the  population  barely  doubled 
(1850-1905),  the  cancer  mortality  increased  more  than  sixfold. 

Next  the  attempt  was  made  to  explain  the  increase  as  due  to  the 
average  age  of  the  population  having  advanced,  and  the  consequent 
liability  of  greater  numbers.  To  this  the  answer  is  that  the  saving  of 
life  in  modern  times  has  mainly  been  confined  to  the  precancerous  years 
^  of  existence,  the  death-rates  of  males  over  thirty-five  and  of  females  over 
forty-five  having  remained  almost  stationary,  while  the  numbers  attaining 
old  age  have  decreased.  Hence  only  an  infinitesimal  fraction  of  the 
increased  cancer  mortality  can  be  thus  accounted  for.  Moreover,  an 
increase  in  the  cancer  mortality  is  by  no  means  a  necessary  corollary  of 
the  survival  of  augmented  numbers  to  the  cancer  age,  as  the  Irish  mor- 
tality statistics  show. 

Another  objection  to  the  reality  of  the  increase  in  cancer  has  been 
raised  by  Dr.  A.  Newsholme  1  and  his  followers.  They  maintain  that  the 
registered  increase  is  only  apparent,  being  due  to  improved  diagnosis 
and  more  careful  death  certification.  There  is,  however,  far  too  much 
uniformity  in  the  steadily  progressive  increments  of  increase,  during  the 
long  succession  of  years,  to  furnish  any  warrant  for  such  a  suggestion ; 
while,  taken  in  its  entirety,  the  increase  is  so  enormous  as  to  make  this 
explanation  seem  quite  far-fetched. 

Moreover,  if  improved  diagnosis  and  death  certification  have  caused 
additions  to  the  cancer  total — which  I  do  not  deny — these  same  condi- 
tions have  also  caused  subtractions  from  it.  Thus,  as  the  Registrar- 
General  tells  us  in  his  fifty-fifth  report,  even  up  to  the  year  1880  such 
common  diseases  as  "  fibroid  tumour,"  "  polypus,"  and  "  lupus,"  were 
1  Proceedings  of  the  Royal  Society,  1893,  vol.  liv.,  p.  209. 


THE  INCREASE  OF  CANCER,  AND  ITS  CONCOMITANTS     53 


TABLE  SHOWING  THE  PREVALENCE  OF  CANCER  AND  ITS  INCREASE 
IN  ENGLAND  AND  WALES. 


Year. 

Total  Popula- 
tion. 

Total 
Deaths. 

Cancer 
Deaths. 

Cancer  Death- 
Rate  per  Mil- 
lion Living. 

Proportion  to 
Population. 

Proportion 
to  Total 
Deaths. 

1840 

15,730,813 

359.687 

2786 

177 

1  to  5646 

1  to  129 

1850 

17,773,324 

368,995 

4966 

279 

1  „  3579 

1  „     74 

1855 

18,829,000 

426,646 

6016 

319 

1  „  3129 

1  „     70 

1860 

19,902,713 

422,721 

6827 

343 

1  „  2915 

1  „     62 

1865 

21,145,151 

490,909 

7922 

372 

1  „  2670 

1  „     62 

1870 

22,501,316 

515,329 

9530 

424 

1  „  2361 

1  „     54 

1875 

24,045,385 

546,453 

11,336 

471 

1  „  2121 

1  „     48 

1880 

25,714,288 

528,624 

13,210 

502 

1  „  1946 

.1  „     40 

1881 

25,974,439 

491,937 

13,542 

520 

1  „  1918 

1  „     36 

1882 

26,413,861 

516,654 

14,057 

532 

1  „  1879 

1  „     36 

1883 

26,770,744 

522,997 

14,614 

546 

1  „  1763 

1  „     35 

1884 

26,922,192 

530,828 

15,192 

564 

1  „  1772 

1  „     35 

1885 

27,220,706 

522,750 

15,560 

572 

1  „  1749 

1  „     33 

1886 

27,522,532 

537,276 

16,243 

590 

1  „  1694 

1  „    33 

1887 
1888 

27,827,706 
28,136,258 

530,758 
510,971 

17,113 

t 

17',506 

615 
621 

1  „  1626 
1  „  1607 

1  „     31 
1  „     29 

1889 

28,448,239 

518,353 

18,654 

656 

1  „  1525 

1  «     30 

1890 

28,762,287 

562,248 

19,433 

676 

1  „  1480 

1  „     28 

1891 

29,081,047 

587,925 

20,117 

692 

1  „  1445 

1  „     29 

1892 

29,405,054 

559,684 

20,353 

690 

1  „  1445 

1  „     27 

1893 
1894 

29,731,100 
30,060,763 

569,958 

498,827 

21,135 
21,422 

711 
713 

1  „  1407 
1  „  1403 

1  „     27 
1  „     23 

1895 

30,383,047 

568,997 

22,945 

755 

1  „  1324 

1  „     24 

1896 

30,717,355 

526,727 

23,521 

764 

1  „  1306 

1  „     22 

1897 

31,055,355 

541,487 

24,443 

787 

1  „  1270 

1  „     22 

1898 

31,397*078 

552,141 

25,196 

802 

1  „  1246 

1  „     22 

1899 

31,907,762 

581,799 

26,325 

825 

1  „  1212 

1  „     22 

1900 

32,261,013 

587,830 

26,731 

828 

1  „  1207 

1  „     22 

1901 

32,621,263 

551,585 

27,487 

842 

1  „  1186 

1  „     20 

1902 

32,997,626 

535,538 

27,872 

844 

1  „  1183 

1  „     19 

1903 

33,378,338 

514,628 

29,089 

872 

1  „  1174 

1  „     17 

1904 

33,763,434 

549,784 

29.682 

877 

1  „  1138 

1  „     18 

1905 

34,152,977 

520,031 

30,221 

885 

1  „  1131 

1  „     17 

54 


THE  NATURAL  HISTORY  OF  CANCER 


usually  classed  as  cancer.  In  like  manner,  many  other  morbid  states, 
formerly  often  regarded  as  cancerous,  are  now  relegated  to  other  cate- 
gories. It  is  hardly  likely,  then,  that  there  is  any  validity  in  Newsholme's 
contention ;  which,  as  I  will  now  proceed  to  show,  is — in  its  main  conten- 
tion  a  statistical  sophism,  based  upon  fallacious  figures  as  well  as  upon 

fallacious  reasoning. 

It  is  claimed  that  there  has  been  no  increase  in  the  registered  cancer 
mortality,  for  those  parts  of  the  body  in  which  the  disease  is  readily 
"  accessible,"  and  therefore  presumably  easy  of  diagnosis,  such  as  the 
uterus,  the  mamma,  the  tongue,  the  mouth,  etc.  ;  whereas,  in  ''  inac- 
cessible "  localities,  such  as  the  stomach,  the  liver,  and  the  intestines, 
where  diagnosis  is  presumed  to  be  difficult,  the  increase  is  said  to  have 
been  very  marked. 

With  regard  to  this,  I  have  to  remark  that,  although  cancer  is  a  disease 
which  often  presents  great  diagnostic  difficulties  in  the  earlier  stages  of 
its  course ;  yet,  before  the  fatal  termination  is  reached,  such  unmis- 
takable signs  as  to  the  real  nature  of  the  malady  usually  appear,  as  pre- 
clude the  very  frequent  occurrence  then  of  erroneous  diagnosis.  The 
very  large  proportion  of  mistaken  diagnoses  in  the  cases  tabulated  by  the 
Cancer  Research  Fund,1  by  Bellinger  etc.,  simply  show  that  these  were 
specially  selected  lots  of  difficult  hospital  cases ;  and  they  cannot  be 
regarded  as  being  in  any  way  typical  of  everyday  experience.  The 
diagnosis  of  advanced  cancer  is,  indeed,  generally  not  a  very  difficult 
matter,  as  compared  with  most  diseases. 

In  support  of  this  "  no  increase  "  hypothesis,  reference  has  been 
made  to  some  data  derived  from  the  Scottish  Widows'  Life  Assurance 
Society,  and  to  mortality  statistics  of  Frankfort ;  but,  as  Dr.  J.  F.  Payne  2 
has  pointed  out,  these  seem  to  be  a  very  inadequate  basis  on  which  to 
raise  such  a  superstructure.  Before  accepting  any  such  conclusion,  we 
must  inquire  whether  similar  results  are  arrived  at  in  larger  populations, 
and  under  more  representative  conditions.  In  the  Report  of  the  Registrar- 
General  for  1889,  a  table  is  given  with  the  object  of  determining  this  very 
question,  by  analysing  a  certain  representative  selection  of  the  deaths 
from  cancer,  during  the  years  1868  and  1888  respectively.  The  results 
thus  obtained  with  regard  to  localization  may  be  epitomized  as  follows  : 


MALES. 

FEMALES. 

Per  100  Deaths  from  Mali 

jnantDis 

ease. 

Per  100  Deaths  from  Malignant  Dis 

jase. 

Stomach 

1868. 
35'3 

1888. 
24'0 

I      1868. 
Uterus      .  .          .  .            .        38'0 

1888. 
31-4 

Liver 
Tongue  and  mouth 
Rectum   .  . 
Face         .  .          i  ! 
Intestine  (ex  rectum) 
All  others 

12'0 

8-0 
7-8 
6'3 
4-0 
26-6 

14-9 

7'2 
8'9 
3'2 
6'6 
35'2 

Mamma   .  .          .  .            .        24'2 
Stomach  .  .          ..                     H'9 
Liver  and  gall-bladder                6'4 
Rectum    .  .          .  .                       3'7 
Intestine  (ex  rectum)                 2'1 
All  others            .  .                     13'7 

18'3 
1T9 
12-7 

4-8 
5'3 
15-6 

lOO'O 

100-0 

lOO'O 

lOO'O 

1  Sci.  Hep.,  No.  2,  part  i.,  1905,  p.  18. 


2  Lancet,  vol.  ii.,  1897,  p.  765. 


THE  INCREASE  OF  CANCER,  AND  ITS  CONCOMITANTS      55 

The  net  result  of  this  inquiry  is  to  show,  that  the  increase  of  the  disease 
has  not  been  confined  to  one  or  to  some  few  parts  of  the  body,  but  that 
it  has  involved  them  all.  It  is  specially  noticeable  that  cancer  of  the 
stomach,  the  chief  representative  of  the  "  inaccessible  "  group,  shows 
less  relative  augmentation,  especially  in  males,  than  any  other  local 
variety  of  the  disease  ;  and  in  both  sexes,  the  death-rates  from  this  form 
of  cancer  show  less  increase  than  those  for  cancer  in  general.  Thus,  in 
1868,  the  death-rate  for  cancer  of  the  stomach  per  1,000,000  living,  thirty- 
five  years  old  and  upwards,  was,  for  males,  283-65,  and  for  females  193-45  ; 
whereas  in  1888,  the  figures  were,  for  males,  346-15,  and  for  females 
277-75.  Thus,  the  increase  for  males  in  the  twenty  years  was  22  per 
cent.,  and  for  females  44  per  cent.  ;  but,  during  the  same  period,  the 
death-rate  for  cancer  in  general  increased  50  per  cent. 

If  we  compare  modern  statistics  as  to  the  site  incidence  of  the  disease, 
with  older  data  collected  by  Marc  d'Espine  (Geneva,  1838-1855),  and 
by  Virchow  (Wiirzbourg,  1852-1855),  the  localization  ratios  are  seen 
to  be  very  similar.  Thus,  d'Espine's  statistics  show  63-3  per  cent,  of 
digestive-system  cancer  (stomach,  45 ;  liver  etc.,  12 ;  intestines  and 
rectum,  6-3);  Virchow's  50-5  (stomach,  34-9;  intestines,  8-1 ;  liver  etc.,  7-5). 
With  these  the  Registrar-General's  data  for  1900,  may  be  contrasted,  the 
total  for  the  digestive  system  being  49  per  cent,  (stomach,  21-5 ;  liver,  14-1 ; 
rectum,  7-1  ;  intestines,  6-3).  There  is  here  no  sign  of  any  specially  dis- 
proportionate increase  of  cancer  of  the  digestive  system ;  and  it  is  the 
same  with  the  other  chief  local  seats  of  the  disease — uterus  18-5  per 
cent.  (Virchow),  15  (d'Espine),  and  11-2  (Registrar-General,  1900)  etc. 

So  far,  therefore,  as  these  analyses  go,  Newsholme's  postulates  are 
shown  to  be  untenable.  Since  the  year  1897,  Dr.  Tatham  has  introduced 
into  the  Registrar-General's  Annual  Reports,  a  table  showing  the  localiza- 
tion of  the  disease  for  each  year.  Analysis  of  these  tables,  for  the  years 
1897  and  1900  respectively,  gives  the  following  results  : 


MALES. 

FEMALES. 

Per  100  Deaths  from  Malignant  Disease. 

Per  100  Deaths  from  Malignant  Disease. 

1897. 

1900. 

1897. 

1900. 

Stomach 

20'  6 

20-5 

Uterus      . 

23-5 

22-5 

Liver 

14-2 

13-9 

Breast      . 

15-5 

15-8 

Rectum    .  .          .  .               i       8'6 

9-0 

Stomach  . 

11-3 

13-8 

Tongue  and  mouth             j       6'3 

6-8 

Liver 

13'2 

14-3 

Intestine  (ex  rectum) 

6'3 

7'0 

Rectum    . 

5'2 

5'2 

(Esophagus 

5'7 

5'4 

Intestine  (ex  rectum,) 

5-2 

5'7 

Bladder    .. 

3-3 

2-8 

Ovary 

1*7 

T7 

Jaws 

3-0 

23 

(Esophagus 

T4 

11 

Neck 
Pharynx,  tonsils,  etc.   . 

2'7 
2'3 

2-3 
2-2 

Tongue  and  mouth 
Bladder    .. 

11 

0-8 

0-6 
0'9 

Larynx  and  trachea 

1-8 

2-0 

Jaws 

0-6 

0-6 

Testis  and  penis 

1-5 

T5 

Neck 

0-6 

0'5 

76-3 

75-7 

82'3 

82'9 

All  others 

23-7 

24-3 

All  others 

17'7 

17-1 

100-0 

100-0 

100-0 

lOO'O 

56  THE  NATURAL  HISTORY  OF  CANCER 

The  general  tenour  of  these  results,  accords  with  that  shown  in  the 
preceding  analysis.  The  proportionate  localization  ratios  show  that  there 
has  been  no  special  increase  in  the  "  inaccessible  "  manifestations  of  the 
disease  ;  and  this  is  very  noticeable  in  such  organs  as  the  .stomach  and 
liver,  which  comprise  the  great  majority  of  this  form  of  the  disease. 
Here  again,  then,  Newsholme's  hypothesis  is  shown  to  be  devoid  of  solid 
foundation. 

Further  confutation  of  this  hypothesis  comes  from  the  work  of 
Dr.  Claud  Muirhead,  the  medical  officer  of  the  Scottish  Widows'  Life 
Assurance  Society,1  who  found  that  the  cancer  death-rate  among  the 
assured  males,  was  nearly  twice  as  great  in  1881-1890,  as  it  was  in  1861- 
1870.  In  a  society  of  this  kind,  whose  members  can  command  the 
services  of  highly  skilled  medical  men,  it  is  hardly  likely  that  such  a  great 
increase  could  be  due  to  improved  diagnosis  and  death  certification, 
especially  as  every  death,  where  there  was  a  suspicion  of  cancer,  was 
carefully  investigated.  "  I  think  it  is  evident,"  says  Muirhead,  "  that 
the  theory  that  this  large  increase  was  wholly  or  even  largely  caused 
by  sudden  increase  of  diagnostic  skill  among  the  class  of  medical  men 
who  certify  causes  of  death  to  this  society,  is  untenable."  This  conten- 
tion is  fully  endorsed  by  an  examination  of  the  localization  ratios  in  512 
fatal  cases,  in  which  the  exact  site  of  the  disease  was  specified.  From 
this  it  appears  that  the  deaths  from  malignant  disease  of  "  inaccessible  " 
parts  (stomach,  liver,  etc.)  decreased  by  7-70  per  cent,  from  1874-1880  to 
1888-1894  ;  and  the  results  thus  obtained  by  comparing  the  percentages 
of  actual  deaths,  were  entirely  in  accord  with  those  arrived  at  by  com- 
paring the  respective  death-rates.  Thus  the  reality  of  the  increase  of  the 
disease  among  the  members  of  this  society,  was  clearly  demonstrated. 

I  find  it  quite  impossible  to  believe  that  anything  like  the  great 
increase  in  the  cancer  mortality,  indicated  by  the  foregoing  table,  can  be 
accounted  for  by  improved  diagnosis,  by  more  accurate  death  certifica- 
tion, by  changes  in  classification,  or  by  alterations  in  the  age  and  sex 
distribution  of  the  population  etc. 

In  this  connexion,  some  valuable  evidence  has  lately  been  adduced 
by  Dr.  F.  L.  Hoffman,  statistician  to  the  Prudential  Insurance  Com- 
pany of  America.2  He  has  found,  for  instance,  that  in  Rhode  Island, 
during  the  period  from  1876-1880  to  1896-1900,  cancer  of  the  breast 
among  women  increased  by  115  per  cent. ;  and  in  the  city  of  Philadelphia 
the  same  malady,  during  the  period  from  1861-1865  to  1896-1900,  in- 
creased 179  per  cent.  Here  there  can  be  no  question  as  to  the  disturbing 
influence  of  sex  diversities,  nor  of  "  inaccessible "  localization  etc. 
Neither  is  there  any  known  marked  alteration  in  the  age  distribution 
of  these  women,  that  would  account  for  this  increase. 

Another  consideration  of  similar  import  is,  that  the  increased  cancer 
mortality  has  been  diffused  all  over  the  country,  instead  of  being  limited 
to  certain  areas  only ;  so  that  those  localities  which  formerly  had  the 
highest,  lowest,  and  average  cancer  death-rates,  still  preserve  their  dis- 

1  "  The  Causes  of  Death  among  the  Assured  in  the  Scottish  Widows'  Life  Assurance 
Society,"  p.  13.     Edinburgh,  1902. 

2  Journal  of  the  American  Medical  Association,  October  19,  1901,  p.  101. 


THE  INCREASE  OF  CANCER,  AND  ITS  CONCOMITANTS     57 

tinction  in  this  respect,  although  the  cancer  mortality  has  everywhere 
augmented.  Taking  all  these  facts  into  consideration,  there  can,  then, 
be  no  doubt  as  to  the  reality  of  the  increase  in  the  cancer  mortality. 
When,  therefore,  Dr.  Bashford  says  :  *  "  There  is  nothing  in  the  statistical 
investigations  of  the  Imperial  Cancer  Research  Fund,  which  points  to  an 
actual  increase  in  the  death-rate  from  cancer :"  I  reply,  that  investigations 
conceived  and  executed  in  such  an  exceedingly  faulty  and  imperfect 
manner,  as  those  referred  to,  could  not  be  expected  to  yield  results  having 
any  scientific  validity. 


The  Disproportionate  Increase  among  Men. 

The  Registrar-General's  Annual  Reports  show  that  more  women  die 
from  malignant  disease  than  men,  and  this  has  been  the  case  ever  since 
these  reports  were  first  issued  (1839).2  In  the  year  1900,  this  disease  was 
fatal  to  16,246  females  and  to  10,475  males.  For  females  the  death- 
rate  was  975  per  1,000,000  living  of  that  sex,  for  males  672.  In  other 
words,  1  in  15  of  all  men,  and  1  in  9  of  all  women,  thirty-five  years  old 
and  upwards,  eventually  died  of  cancer.  The  cancer  mortality  among 
males  in  that  year,  exceeded  the  decennial  average  for  the  male  sex  by 
16  per  cent. ;  and  among  females  by  10  per  cent.  Attention  is  thus 
drawn  to  the  remarkable  fact,  that  the  increasing  cancer  mortality  is 
affecting,  and  for  many  years  has  affected,  males  to  a  much  greater 
extent  than  females.  The  difference  between  the  sexes  in  respect  to 
their  proclivity  to  malignant  disease,  has  thus  been  steadily  diminishing 
ever  since  1850,  as  is  shown  by  the  following  table  : 

TABLE  SHOWING  THE  INCREASE  OF  MALIGNANT  DISEASE  AMONG 
MALES  AND  FEMALES  PER  MILLION  LIVING. 


Period. 

Male  Cancer  Death-rate. 

Female  Cancer  Death-               ee_. 
rate. 

Ratio. 

i 

1851  t 

o  1860 

195 

434                              It 

o2'2 

1861 

1870 

244 

523                              1 

,  2-1 

1871 

1880 

315 

622                              1 

,  T9 

1881 

1890 

430 

739                              1 

,  T7 

1891 

1900 

597 

903                              1 

,  1'5 

1901 

1905 

723 

997                              1 

1 

,  1-3 

It  thus  appears  that,  although  there  has  been  a  great  increase  of 
malignant  disease  in  both  sexes  during  the  last  half -century,  and  although 
at  the  present  time  more  women  are  affected  than  men,  yet  the  malady 
has  augmented  much  more  rapidly  among  the  latter  than  among  the 
former.  Moreover,  it  is  noticeable  that  the  average  age  of  English 
women  is  higher  than  that  of  men,  so  that  the  death-rates,  as  given 
above,  are  unduly  favourable  to  the  female  sex. 

It  seems  likely,  if  this  disproportionate  increase  of  cancer  among 
males  is  not  checked,  that  the  disease  will  soon  be  as  prevalent  among 

1  Set.  Hep.,  No.  2.  part  i.,  1905. 

2  In  1838.  620  males  and  1,828  females  died  of  cancer,  the  respective  death-rates  being 
84  for  males  and  240  for  females,  or  1  male  to  2'74  females. 


58  THE  NATURAL  HISTORY  OF  CANCER 

men  as  among  women ;  or  the  comparative  proclivity  of  the  sexes  in  the 
respect  may  be  reversed,1  as  has  already  happened  in  a  few  countries — 
e.g.,  Australia,  New  Zealand  etc. 

The  greater  prevalence  of  malignant  disease  among  women,  is  entirely 
due  to  the  frequency  with  which,  in  them,  the  mammae  and  uterus  are 
affected,  the  corresponding  structures  in  males  very  rarely  originating 
the  disease  ;  while,  in  all  other  localities,  the  male  liability  is  the  greater. 

Here  it  may  be  noted  that  the  comparative  proclivity  of  women  to 
non-malignant  tumours  and  cysts,  is  even  more  considerable  than  it  is 
to  cancer ;  and  this  also  arises  from  the  fact  that,  in  them,  the  reproductive 
organs,  especially  the  uterus  and  ovaries,  very  frequently  originate 
tumours  of  this  kind,  whereas  the  corresponding  male  organs  are  seldom 
affected. 

Another  point  worthy  of  notice  in  this  connexion  is  that,  for  both 
sexes,  the  percentage  of  cancer  deaths  at  ages  above  forty-five  is  greater 
than  it  used  to  be,  the  disproportionate  increase  in  the  male  cancer 
mortality  being  mainly  due  to  excessive  incidence  of  the  disease  at 
comparatively  advanced  ages. 

If  now  we  ask,  What  is  the  cause  of  this  disproportionate  increase  of 
cancer  among  men  ?  Newsholme,  De  Bovis,  and  others  reply  :  There 
has  been  no  real  increase,  but  the  apparent  augmentation  is  due  to 
improved  diagnosis  and  death  certification,  owing  to  the  majority  of 
cancers  in  men  being  of  the  "  inaccessible  "  variety,  which  is  difficult  to 
discriminate.  As  I  have,  in  the  foregoing  remarks,  fully  exposed  the 
fallaciousness  of  this  hypothesis,  I  need  not  further  revert  to  the  matter 
here. 

It  seems  to  me  probable  that  this  undue  incidence  of  the  increasing 
cancer  mortality  in  men,  may  be  ascribed  to  the  fact  that  of  late,  as  the 
^result  of  urbanization,  the  conditions  of  life  for  men  have  come  to  resemble 
more  closely  those  for  women  than  heretofore.  It  is  undeniable  that 
urbanization  has  affected  far  more  profoundly  the  natural  life  of  men — 
altering,  modifying,  and  suppressing  their  ancestral  habits — than  it  has 
the  natural  life  of  women.  Out  of  these  conditions,  which  comprise  a  more 
domesticated  mode  of  life,  want  of  proper  exercise,  and  excess  of  food, 
I  believe  the  present  increased  cancer  mortality  has  sprung. 


The  Concomitant  Decline  of  Tubercle. 

Cancer  is  a  disease  more  to  be  dreaded  than  tubercle,  under  the  con- 
ditions of  existence  at  present  obtaining  in  modern  communities  where 
the  occidental  type  of  civilization  prevails ;  for,  while  tubercle  has  declined 

1  During  the  twenty  years  comprised  between  the  decennia  1851-1860  and  1871-1880, 
the  increase  for  males  was  at  the  rate  of  2'4  per  cent,  per  annum,  and  for  females  1'8  per 
cent,  During  the  period  between  1861-1870  and  1891-1897  the  annual  average  increase 
for  males  was  3'1  per  cent.,  and  for  females  T9  per  cent.  "  Should  equal  percentages  of 
increase  be  maintained,  they  would  bring  up  the  cancer  mortality  rate  to  1871  per  million, 
for  both  males  and  females  about  the  year  1932 ;  and  thereafter  the  rate  for  males  would 
exceed  that  for  females  "  (Tatham).  The  same  disparity  is  shown  if  we  restrict  our 
neld  to  persons  aged  thirty-five  and  upwards  ;  thus,  in  1885,  1  in  21  men,  and  1  in  12 
women  of  this  age  limit,  eventually  died  of  cancer  ;  whereas,  in  1905,  the  corresponding 
figures  were  1  in  12  men,  and  1  in  8  women. 


THE  INCREASE  OF  CANCER,  AND  ITS  CONCOMITANTS      59 


with  great  rapidity,  cancer  has  increased  at  a  still  faster  rate,  and  these 
inversely  related  changes  are  still  in  active  progress.  In  illustration  of 
these  remarks,  it  may  be  mentioned  that  during  the  last  half  of  the 
nineteenth  century,  the  cancer  mortality  for  our  country  tripled ;  while, 
during  the  same  period,  the  tubercle  death-rate  declined  to  the  extent 
of  nearly  one-half.  If  we  extend  our  survey,  so  as  to  embrace  the  sixty- 
five  years  from  1838  to  1903,  these  peculiarities  are  rendered  still  more 
evident ;  for,  during  this  period,  the  increase  in  the  cancer  mortality  was 
more  than  fivefold— viz.,  from  16  per  100,000  living  in  1838,  to  87  in  1903 ; 
whereas  the  phthisis  mortality,  in  the  same  time,  decreased  more  than 
threefold — viz.,  from  380  in  1838,  to  119  in  1903.  Moreover,  the  latest 
ascertained  cancer  death-rate  (88  for  1905)  is  the  highest  on  record  ; 
while  that  for  phthisis  (114  in  1905)  is  the  lowest. 

Cancer  is  now  a  more  fatal  disease  for  women  than  phthisis,  the 
respective  death-rates  for  1905,  being  100  for  the  former  and  94  for  the 
latter  malady ; l  it  was  in  1903  that  cancer  first  gained  this  lead. 

Unless  some  great  change  in  the  national  habits  soon  takes  place,  of 
which  there  is  at  present  no  well-marked  indication,  cancer  will  ere  long 
claim  more  victims  even  than  phthisis,  as  is  already  the  case  in  many 
localities — e.g.,  Hampstead,  Clifton,  Bath  etc. 

This  great  decline  in  the  tubercle  mortality  under  modern  conditions 
of  existence,  is  one  of  the  most  remarkable  and  unexpected  facts  that  the 
study  of  vital  statistics  has  revealed  ;  and,  rightly  apprehended,  it  throws 
a  striking  light  on  the  problem  of  the  increase  of  cancer. 

This  correlated  variability  in  morbid  proclivity  is  met  with  in  every 
community,  where  the  modern  type  of  civilization  prevails ;  for  in  those 
parts  where  apparent  exceptions  occur,  as  in  some  districts  of  Ireland, 
this  type  of  civilization,  with  its  material  prosperity,  good  food,  and  good 
sanitation,  is  conspicuous  by  its  absence,  as  I  have  ascertained  by  per- 
sonal investigation  on  the  spot,  with  regard  to  Kerry  and  the  "  Wild 
West  "  of  Ireland. 

In  point  of  time,  these  two  movements  have  been  coeval,  as  is  shown 
by  the  following  table,  indicating  the  respective  death-rates  per  million 
living,  during  the  latter  half  of  the  nineteenth  century  : 


1851-1860. 

1861-1870. 

1871-1880. 

1881-1890. 

1891-1900. 

Cancer 

317 

384 

468 

589 

754 

Phthisis     

2676 

2475 

2116 

1724 

1391 

Other  tuberculous  diseases 

807 

765 

,47 

696 

619 

This  table  shows  that,  for  the  country  as  a  whole,  the  incidence  of 
cancer  and  tubercle  vary  inversely. 

It  is  a  curious  fact,  that  in  many  other  of  the  inter-relations  of  these 
two  diseases,  an  inverse  relationship  is  also  noticeable,  as  I  shall  have 
occasion  to  indicate  in  the  sequel. 

In  this  country  a  comparatively  high  and  increasing  cancer  mortality 

1  The  cancer  death-rates,  for  1905,  are  75'6  for  males  and  100'5  for  females  ;  the  corre- 
sponding phthisis  rates  being,  for  males,  134" 7  and,  for  females,  94'7. 


60 


THE  NATURAL  HISTORY  OF  CAXCER 


implies,  according  to  its  extent,  a  comparatively  low  and  decreasing 
tubercle  mortality,  and  vice  versa. 

A  similar  connexity  is  noticeable,  even  where  we  confine  our  attention 
only  to  certain  limited  areas,  as  Haviland  *  has  very  clearly  demonstrated. 
He  worked  out  the  death-rates  for  each  of  these  diseases,  for  every  one 
of  the  630  registration  districts,  with  such  corrections  for  age  and  sex 
distribution  as  the  available  data  permitted.  He  proceeded  to  indicate 
on  each  of  two  identical  maps,  the  varying  death-rates  from  each  malady, 
by  colouring  the  different  areas  —  blue  for  those  above  the  average,  and 
red  for  those  below,  with  intermediate  tints  for  the  corresponding  degrees 
of  mortality.  Having  completed  this  laborious  task,  he  found,  on  com- 
paring the  two  maps,  that  just  such  inter-relations  as  those  above  men- 
tioned, prevailed  in  almost  every  district. 

Some  years  ago,  William  Farr2  selected  thirteen  registration  districts, 
widely  separated  from  one  another,  as  examples  of  the  favourable  influence 
of  improved  sanitation,  good  drainage,  and  good  water-supply  on  the 
public  health.  During  the  three  decennia  over  which  this  inquiry 
extended,  all  the  selected  districts  showed  progressive  declines  in  the 
general  death-rate,  as  well  as  in  the  tubercle  mortality  ;  yet,  in  spite  of 
these  gains,  the  cancer  death-rates  were  shown  to  have  markedly  in- 
creased, in  every  one  of  these  thirteen  districts. 

Within  the  limits  of  individual  large  towns,  as  I  shall  presently  have 
occasion  to  prove,  a  similar  state  of  affairs  is  almost  everywhere  notice- 
able. Where  the  population  is  densest,  there  the  tubercle  mortality  is 
highest  ;  and  it  is  just  in  these  densely  populated  areas  that  the  cancer 
mortality  is  lowest. 

The  increase  of  cancer  and  the  decrease  of  phthisis  in  London  during 
the  latter  half  of  the  nineteenth  century,  are  shown  by  the  following 
data  •  3 


1851  to  1860 
1861  „  1870 
1871  „  1880 
1881  „  1890 
1891  „  1900 


Cancer  Death-rate  Phthisis 

per  100,000  Living.      Death-rate. 


286 
284 
251 
209 
183 


For  subsequent  years  the  figures  are  : 


1901 
1902 
1903 
1904 
1905 


..  96 

..  92 

.  93 


171 
160 
155 
162 
142 


The  Report  of  the  Medical  Officer  of  Health  for  1903,  shows  that  well- 
to-do,  salubrious  Hampstead  has  the  highest  cancer  death-rate  of  any 
Metropolitan  borough— viz.,  120  per  100,000  living*— while  its  death- 

"  Geographical  Distribution  of  Disease  in  Great  Britain,"  2nd  edit.,  1892  ; 
earlier  work,      Geography  of  Heart  Disease,  Cancer,  and  Phthisis,"  1875 
•  Registrar-General's  Thirty-seventh  Annual  Report. 
Report  of  the  Medical  Officer  of  Health  of  the  County  of  London  for  1903. 
Corrected  for  age  and  sex  distribution,  for  hospitals,  etc. 


THE  INCREASE  OF  CANCER,  AND  ITS  CONCOMITANTS     61 


rate  from  phthisis  is  the  lowest — viz.,  73.  Next  to  Hampstead,  the 
wealthy  communities  of  Marylebone  (comprising  some  of  the  best  resi- 
dential quarters  of  the  West  End),  and  Chelsea  suffer  most  from  cancer, 
their  respective  death-rates  from  this  cause  being  119  and  106  ;  while 
their  mortality  from  phthisis  is  decidedly  below  the  average  (155) — viz., 
151  and  149  respectively. 

Of  the  six  metropolitan  boroughs  having  the  highest  phthisis  mor- 
tality— viz.,  Holborn,  Shoreditch,  Southwark,  Finsbury,  Bethnal  Green, 
and  Stepney — only  one,  Southwark,  has  a  cancer  death-rate  above 
average  (96),  its  figure  being  104,  and  this  is  an  exceptional  occurrence. 

Wands  worth,  with  a  cancer  death-rate  of  102,  has  the  low  phthisis 
death-rate  of  96. 

As  another  example  of  this  connexity,  the  case  of  Bristol  may  be 
instanced,  with  its  well-to-do  and  salubrious  suburb  Clifton,  and  its  busy 
working-class  and  comparatively  poor  district  of  St.  Philip,  for  which  the 
respective  mortality  data  in  1903,  were  as  follows  : 


Bristol. 

Clifton. 

St.  Philip. 

Total  population 
Total  deaths      
General  death-rate 

338,895 
4822 
142 
281 

44,435 
494 
111 
46 

48,986 
711 
145 
38 

Cancer  death-rate 
Phthisis  deaths 
Phthisis  death-rate       .            .            .  .            .' 

83 
366 
103 

103 
29 
65 

77 
55 
110 

In  nearly  all  modern  communities  where  statistical  data  are  pub- 
lished, similar  relations  prevail  between  these  two  diseases,  of  which  I 
shall  subsequently  have  occasion  to  cite  many  instances.  Thus,  Hungary, 
with  the  lowest  cancer  death-rate  of  any  country  in  Europe  (33),  has  the 
highest  tubercle  mortality  (387).  International  vital  statistics  are,  how- 
ever, at  present  in  too  backward  a  condition  to  enable  us  to  make  a 
really  satisfactory  study  of  these  inter-relations  in  every  community. 
Thus,  for  France,  Denmark,  and  Sweden,  the  available  data  refer  only  to 
the  town  population,  which  in  these  communities  comprises  only  a  small 
part  of  the  total  population  ;  then,  as  to  Switzerland,  there  are  no  official 
data  for  the  whole  country.  Moreover,  several  communities  are  now  in 
such  a  state  of  acute  transition,  owing  to  the  sudden  swarming  to  the 
towns  etc.,  as  to  render  their  vital  statistics  for  the  time  being  unreliable 
for  such  comparisons. 

In  this  connexion  it  is  worth  noting  that  the  increase  of  cancer  and 
the  decline  of  tubercle,  seem  to  have  set  in  earlier  in  Great  Britain  than 
in  other  countries.  Moreover,  the  British  vital  statistics  are  unusually 
complete  and  accurate  with  regard  to  these  matters  ;  and  they  have  the 
further  great  advantage  of  having  been  compiled  on  a  uniform  plan,  for 
a  long  series  of  years. 

I  regard  this  decline  in  the  prevalence  of  tuberculous  disease,  as  the 
direct  outcome  of  the  better  food  and  improved  hygienic  conditions,  for 
which  we  are  indebted  to  our  increased  national  prosperity  ;  and  I  shall 
endeavour  to  show  that  conditions  of  this  kind,  by  their  action  in  another 


62  THE  NATURAL  HISTORY  OF  CANCER 

direction,  are  also  mainly  responsible  for  the  augmented  cancer  mor- 
tality. 

Moreover,  it  seems  to  me  exceedingly  probable,  from  considerations 
derived  mainly  from  the  study  of  the  family  history  of  cancer  patients, 
that  many  of  those  thus  saved  from  tubercle,  eventually  perish  from 
cancer.  Indeed,  I  think  the  increase  in  the  latter  disease  has  largely 
been  brought  about  in  this  way. 

Indigence,  insufficiency  of  food,  overcrowding,  and  bad  sanitation, 
which  favour  the  generation  of  most  diseases,  especially  tuberculous  and 
contagious  affections,  exercise  no  such  power  over  the  incidence  of  cancer, 
which  flourishes  most  under  just  the  opposite  conditions. 

Etiological. 

The  precise  period  at  which  these  remarkable  changes  in  the  morbid 
proclivities  of  the  population  commenced,  probably  dates  back  tp  the 
latter  part  of  the  eighteenth  century  ;  at  any  rate,  they  were  certainly 
in  operation  during  the  whole  of  the  nineteenth  century. 

It  is  in  the  spread  of  industrialism  that  their  origin  will  be  found, 
and  especially  in  that  particular  phase  of  it,  characterized  by  the  utiliza- 
tion of  steam  as  a  motive  power. 

This  kind  of  progress  has  entailed  two  remarkable  effects  :  (1)  urbaniza- 
tion, the  most  stupendous  environmental  change  that  the  human  race  has 
ever  experienced  ;  and  (2)  enormous  increase  of  riches  with  widespread 
material  prosperity. 

It  now  remains  for  me  to  show  how,  by  the  interaction  of  these 
factors,  cancer  has  increased,  while  tubercle  and  other  maladies  have 
markedly  diminished. 

1.  It  is  generally  agreed  that  the  stability  of  the  equilibration  of  the 
•y^  constituent  elements  of  living  bodies,  is  more  profoundly  affected  by 
sudden  and  violent  changes  in  the  environment,  than  by  any  other  group 
of  circumstances.  The  invariable  tendency  of  such  changes  is  to  render 
the  organisms  that  survive  them  more  plastic — that  is  to  say,  more  prone 
to  deviate  from  the  normal  routine  of  their  growth  and  development. 
The  natural  history  of  cancer  shows  that  it  is  a  disease  belonging  to  this 
category.  Any  sudden,  far-reaching,  environmental  change  of  some 
duration  is  probably  potent  in  this  direction,  as  may  be  inferred  from 
the  undue  proclivity  to  cancer  of  immigrants  into  the  United  States, 
Australia,  New  Zealand,  etc.,  to  which  I  have  previously  called  atten- 
tion ;  and  there  are  good  reasons  for  believing,  as  I  shall  subsequently 
have  occasion  to  indicate,  that  the  sudden  change  from  poverty  and 
want,  to  riches  and  plenty  may,  per  se,  be  equally  potent — e.g.,  Switzer- 
land, Denmark  etc. 

The  nineteenth  century  has  been  variously  called  the  age  of  steam, 
the  age  of  iron,  the  age  of  factories  and  industrialism,  the  age  of  natural 
science,  the  age  of  the  microscope  and  of  the  microbe,  according  to  the 
standpoint  of  the  individual  observers  ;  but,  for  the  great  majority  of  the 
Western  world,  the  past  century  will  for  ever  be  memorable  as  the  age  of 
urbanization.  This  tremendous  vicissitude,  suddenly  precipitated,  un- 


THE  INCREASE  OF  CANCER,  AND  ITS  CONCOMITANTS     63 

doubtedly  constitutes  the  most  profound  and  far-reaching  environmental 
change,  that  the  human  race  has  ever  experienced  ;  and  in  England,  where 
80  per  cent,  of  the  population  are  now  town-dwellers,  it  has  gone  further 
than  in  any  other  community.  The  last  century  has  witnessed  the 
transition  of  millions  of  people  from  rural  life  and  surroundings,  to  life 
in  large  towns,  where  all  the  conditions  of  existence  are  so  different.  I 
believe  that  the  increase  of  cancer  in  this  country,  has  sprung  out  of 
impulses  thus  determined. 

Until  the  advent  of  the  nineteenth  century  an  open-air  existence  had, 
from  time  immemorial,  been  the  lot  of  the  great  majority  of  EngUsh 
people,  who  depended  for  subsistence  mainly  upon  agricultural  pursuits. 
Since  that  time  this  old-established  mode  of  life  has  been  radically  and 
rapidly  changed. 

The  first  official  enumeration  of  the  population  was  made  in  1801, 
when,  of  the  9,000,000  of  people,  more  than  three-fourths  lived  in  the 
country.  A  century  later,  in  1901,  the  population  had  increased  to  over 
32.500,000,  of  whom  less  than  one-fourth  now  lived  in  the  country. 

In  1801,  there  were  in  England  and  Wales  sixty-one  towns,  with  a 
population  of  2,163,698  inhabitants  ;  in  1851,  these  towns  had  increased 
to  580,  and  their  population  to  6,254,251,  or  35  per  cent,  of  the  entire 
population.  Twenty  years  later,  in  1871,  the  towns  numbered  938,  and 
their  population  was  14,000,000,  or  61  per  cent,  of  the  entire  population  ; 
in  1881,  over  70  per  cent,  of  the  population  was  urban  ;  in  1891  this 
proportion  had  increased  to  nearly  72  per  cent. ;  and,  in  1901,  the  town 
dwellers  comprised  77  per  cent,  of  the  entire  population.  The  urbaniza- 
tion of  the  English  people  is  now  wellnigh  complete,  for  most  of  the 
present  so-called  rural  population  are  suburbanites,  or  immigrants  from 
the  towns.  Moreover,  the  towns  have  now  become  the  chief  breeding- 
grounds  for  the  replenishment  of  the  race,  the  rural  population  having 
lost  its  former  productiveness  in  this  respect. 

Thus,  in  the  course  of  a  comparatively  brief  span,  the  conditions  of 
existence  for  the  whole  nation  have  undergone  more  profound  changes, 
than  hundreds  of  centuries  had  previously  wrought. 

2.  One  of  the  most  potent  and  widespread  effects  of  the  conditions  of 
life  incidental  to  urbanization,  on  the  health  of  those  involved  in  its  influ- 
ence, is  its  tendency  to  induce  degenerative  changes  which  impair  the 
capacity  of  those  affected  to  resist  various  morbid  excitations.  It  will 
probably  be  found  that  these  changes  ultimately  depend  upon  perverted 
cellular  metabolism,  which  is,  I  believe,  the  common  root  whence  spring 
such  diverse  morbid  manifestations  as  tubercle,  cancer,  and  insanity. 

Tubercle  is  a  malady  naturally  tending  to  increase  with  increasing 
density  of  population,  and  especially  with  urbanization.  If,  therefore, 
this  malady  has  not  only  been  arrested,  but  has  immensely  declined,  in 
spite  of  the  rapid  spread  of  urbanization,  there  must  be  some  good 
reason  for  it. 

This  reason  is  sufficiently  obvious.  It  is  the  unexampled  increase  in 
material  prosperity,  which  the  new  conditions  of  existence  have  brought 
with  them.  Prosperity  has  given  our  people  good  food  and  good  sanita- 
tion ;  and  thus  the  evil  tendencies  of  urbanization  have,  to  a  certain 


64  THE  NATURAL  HISTORY  OF  CANCER 

extent,  been  mitigated.  Many  of  those  who  have  acquired  morbid  pre- 
dispositions owing  to  urbanization,  now  escape  the  fate  that  would  have 
overtaken  them  under  other  conditions.  It  would,  however,  be  a  mis- 
take on  this  account  to  regard  such  persons  as  being  normally  constituted. 
Their  degeneracy  is  none  the  less  real  because  it  is  not  obviously  manifest. 
According  to  my  belief,  it  is  from  such  persons  and  their  descendants, 
that  the  ranks  of  the  great  cancer  army  are  being  constantly  recruited. 
This  view  of  the  question  throws  an  interesting  sidelight  on  the  curious 
.'  paradox,  in  which  there  certainly  is  much  truth,  that  a  high  cancer 
mortality  is  an  indication  of  general  prosperity  and  good  sanitary  con- 
ditions. 

Probably  no  single  factor  is  more  potent  in  determining  the  outbreak 
of  cancer  in  the  predisposed,  than  excessive  feeding.  There  can  be  no 
doubt  that  the  greed  for  food  manifested  by  the  people  of  modern  com- 
munities, is  altogether  out  of  proportion  to  the  requirements  of  their 
present  mode  of  life.  Many  indications  point  to  the  gluttonous  con- 
sumption of  proteids — especially  meat — which  is  such  a  characteristic 
feature  of  the  age,  as  likely  to  be  specially  harmful  in  this  respect.  Statis- 
tics show  that  the  consumption  of  meat  has  for  many  years  been 
increasing  by  leaps  and  bounds ;  *  and  it  has  now  reached  the  amazing 
total  of  130  pounds  per  head  per  year  (men,  women,  and  children),  which 
is  nearly  double  what  it  was  half  a  century  ago,  when  the  conditions  of 
life  were  less  incompatible  with  high  feeding.  Among  the  well-to-do 
classes,  the  meat  consumption  has  been  estimated  to  amount  to  from 
180  to  330  pounds  per  head  per  year.  In  addition  to  these  totals,  large 
quantities  of  game,  poultry,  rabbits,  etc.,  must  be  included,  as  well  as  a 
fish  consumption  of  75  pounds  per  head  per  year,  12  pounds  of  cheese, 
14  gallons  of  milk,  and  80  eggs  each  a  year. 

When  excessive  quantities  of  such  highly  stimulating  forms  of  nutri- 
ment are  ingested  by  persons  whose  cellular  metabolism  is  perverted,  it 
seems  probable  that  there  may  thus  be  excited,  in  those  parts  of  the  body 
where  vital  processes  are  still  capable  of  rejuvenescence,  such  excessive 
and  disorderly  cellular  proliferation  as  may  eventuate  in  cancer.  No 
doubt  other  factors  co-operate  besides  those  I  have  already  mentioned, 
and  among  these  I  should  be  inclined  to  name  deficient  exercise,  and 
probably  also  lack  of  sufficient  fresh  vegetable  food. 

Such  influences  as  are  comprised  under  the  terms  alimentation  and 
domestication,  seem  to  me  to  be  of  paramount  importance  in  the  aetiology 
of  cancer. 

With  regard  to  the  influence  of  diet  rich  in  proteids  on  the  incidence 
of  tubercle,  I  think  there  can  be  no  doubt  that  its  effect  is  just  the  con- 
verse of  that  which  we  have  seen  in  the  case  of  cancer.  That  is  to  say, 
when  the  proportion  of  proteids,  especially  meat,  in  the  dietary  is  too 
small,  tubercle  is  very  apt  to  supervene,  even  when  climatic  and  hygienic 
conditions  are  favourable  ;  and,  besides  the  proteids  of  meat,  the  fats 
also  seem  to  have  anti-tuberculous  properties. 

1  Report  of  Committee  of  Royal  Statistical  Society  of  Great  Britain,  December, 
IUU4  ;  tor  other  data  see  also  Mulhall's  great  work,  "  The  Industries  and  Wealth  of 
Nations,"  1896. 


THE  INCREASE  OF  CANCER,  AND  ITS  CONCOMITANTS      65 

As  an  example  of  this,  the  case  of  Ireland  may  be  cited,  where,  as 
indicated  in  the  preceding  chapter,  conditions  of  existence  which  are 
predominantly  rural,  are  associated  with  poverty  and  a  diet  unduly 
deficient  in  proteids.1  Under  these  circumstances,  the  cancer  mortality 
is  much  lower  than  in  England,  while  that  from  tubercle  and  phthisis  is 
much  higher  ;  and  this  in  spite  of  the  more  favourable  climatic  conditions 
and  rural  surroundings.  Moreover,  it  is  significant  that  in  the  "  Wild 
West  " — e.g.,  in  Kerry,  where  these  conditions  are  most  en  evidence,  and 
the  people  are  notoriously  underfed — the  cancer  mortality  is  the  lowest 
in  the  United  Kingdom,  while  the  tubercle  mortality  is  exceedingly 
high. 

Per  contra,  in  the  one  part  of  Ireland  where  industrialism  and  its 
concomitants  have  made  marked  progress,  and  where  material  prosperity 
is  most  noticeable — e.g.,  in  Ulster — the  cancer  death-rate  is  the  highest, 
while  that  from  phthisis  is  comparatively  low. 

In  fact,  the  increased  cancer  mortality  in  Ireland  during  recent  years, 
is  mainly  due  to  the  augmentation  of  the  malady  among  the  industrial 
population  of  Ulster,  Dublin  etc. 

It  now  remains  for  me  to  indicate  briefly  some  of  the  salient  features 
as  to  the  extraordinary  prosperity,  with  which  this  increase  of  cancer  has 
coincided.  It  is  all  the  more  necessary  for  me  to  do  this,  because  some 
pathologists  still  entertain  and  teach  very  erroneous  views  on  this  sub- 
ject. These  have  received  their  apotheosis  from  Sir  W.  J.  Sinclair,2  who 
says  :  "  If  we  could  place  all  the  lower  orders  who  suffer  from  privation 
and  depressing  environment,  for  a  generation  or  two  in  the  position  of 
the  more  favoured,  we  should  stamp  out  cancer." 

As  all  the  information  at  my  disposal  is  totally  opposed  to  any  such 
conclusion,  it  seems  desirable  to  briefly  review  this  evidence. 

During  the  last  half-century  the  wealth  of  the  community  has  more 
than  doubled,  and  is  now  estimated  to  amount  to  15,000  millions  sterling, 
the  annual  income  being  1,750  millions.  The  present  annual  expenditure 
is  estimated  at  1,386  millions,  of  which  468  millions,  or  34  per  cent.,  is 
spent  on  food  and  drink  (Giffen)  ;  and  in  the  case  of  the  working  classes, 
50  per  cent,  of  their  earnings  are  thus  spent.  During  this  period  the 
income-tax  assessments  have  increased  from  300  millions  to  833  millions 
sterling.  This  country  is  still  the  wealthiest  in  the  world,  although  its 
wealth  is  proportionally  less  widely  diffused  among  the  people  than  is 
the  case  in  many  other  countries.  That  the  great  mass  of  our  people 
have,  however,  largely  participated  is  evidenced  by  the  fact  that  the 
accumulated  savings  of  the  working  classes  now  total  531  millions  sterling  ; 
and  by  such  other  considerations  as  I  will  now  proceed  to  mention. 

Pauperism  has  diminished  by  more  than  one-half — viz.,  from  5-3  per 
cent,  of  the  total  population  in  1851  to  2-4  in  1901 — and  it  is  now  less 
than  at  any  previous  period  of  our  history.  Crime,  likewise,  has  steadily 
declined. 

Wages  have  gone  up  as  much  as  from  25  to  50  per  cent. ;  while,  at 

1  In  1895  the  meat  consumption  of  Ireland  was  estimated  by  Mulhall  at  only  40  pounds 
per  head  per  year,  or  barely  a  third  of  the  amount  consumed  in  England. 

2  Allbutt's  "  System  of  Gynaecology,"  1897,  p.  657. 

5 


66  THE  NATURAL  HISTORY  OF  CANCER 

the  same  time,  the  prices  of  aU  the  really  essential  commodities  of  life 
have  fallen  to  an  extraordinary  extent.1 

In  the  same  time  the  consumption  of  meat  per  head  has  more  than 

UThe  general  death-rate  declined  from  22-7  in  1851-1855,  to  18-2  in 
1900,  to  15-2  in  1903  ;  and  the  population  has  steadily  increased. 

The  mortality  from  zymotic,  tuberculous,  and  many  other  diseases, 
has  markedly  diminished,  and  sanitary  conditions  have  greatly  improved. 
In  short,  the  bulk  of  the  people  are  better  paid,  better  housed,  and  better 
fed  than  ever  they  have  been  before — that  is  to  say,  just  such  conditions 
have  prevailed  as  Sinclair  alleges  are  necessary  to  stamp  out  cancer— yet, 
instead  of  having  decreased  during  this  period,  the  cancer  mortality  has 
tripled. 

In  further  support  of  my  contention,  I  would  point  out  that  the 
Registrar-General's  Reports  show  that  the  cancer  mortality  is  lowest  where 
the  conditions  of  life  are  hardest,  the  surroundings  the  most  squalid,  the 
density  of  population  greatest,  the  tubercle  mortality  highest,  the  general 
and  infantile  mortality  highest,  and  where  sanitation  is  least  perfect — in 
short,  among  the  poor  of  the  industrial  classes  in  our  great  towns  ; 
whereas,  among  the  wealthy  and  wrell-to-do,  where  the  standard  of 
health  is  at  its  best,  and  life  is  easiest,  and  where  all  the  conditions 
of  existence  are  just  the  converse  of  the  foregoing,  there  the  cancer 
mortality  is  highest,  as  I  shall  subsequently  have  occasion  to  show  more 
in  detail. 

As  an  indication  in  the  same  direction,  the  experience  of  those  engaged 
in  prisons,  workhouses,  and  lunatic  asylums  may  be  cited ;  which  is  to 
the  effect  that  cancer  is  comparatively  rare  among  the  inmates  of  such 
institutions,  as  it  is  also  among  the  intemperate.  Of  like  import  is  the 
fact  that  cancer  is  so  fearfully  common  in  civilized  communities  ;  whereas, 
among  savages,  it  is  almost  unknown.  Moreover,  in  the  animal  wrorld, 
it  is  among  the  domesticated  varieties  that  malignant  and  other  tumours 
are  usually  met  with  :  in  a  state  of  nature  such  diseases  are  almost 
unknown. 

That  cancer  is  a  disease  of  persons  whose  previous  life  has  been 
healthy,  and  whose  nutritive  vigour  seems  to  promise  long  life,  is  a 
statement  in  which  I  entirely  concur.  Long-continued  observation  of 
cancer  patients,  in  the  early  stage  of  the  disease,  has  convinced  me  that 
most  of  those  affected  are  large,  well-nourished  persons,  who  appear  to 
be  overflowing  with  vitality.  Such  types  are  indicative  of  hypernutri- 
tion.  The  small,  pale,  ill-nourished,  and  overworked  women,  of  the  type 
so  familiar  in  Lancashire  and  other  industrial  centres,  are  seldom  afflicted 
with  this  disease. 

The  natural  functions  of  female  cancer  patients  are  performed  with 
ease  and  regularity.  Their  sexual  health  is  vigorous,  the  capacity  for 
reproduction  beginning  earlier  and  lasting  longer  than  in  the  generality 

1  The  Report  of  the  Royal  Commission  on  Agriculture  (1897)  shows:  "That 
during  the  last  quarter  of  a  century  there  has  been  a  fall  of  over  40  per  cent,  in  the  price 
of  staple  cereals,  which  in  the  case  of  wheat  is  50  per  cent.  ;  that  in  beef  the  fall  has  been 
from  24  to  40  per  cent.,  and  in  mutton  from  20  to  30  per  cent.  ;  in  dairy  produce  the  price 
declined  30  per  cent.  ;  in  potatoes  20  to  30  per  cent.,"  etc. 


THE  INCREASE  OF  CANCER,  AND  ITS  CONCOMITANTS   67 

of  women.  Just  so  is  it  with  regard  to  marriage,  for  a  greater  propor- 
tion of  these  cancer  patients  marry  than  of  the  female  population  in 
general.  Moreover,  they  marry  earlier,  and  commence  to  have  children 
sooner,  than  the  generality  of  married  women  ;  and  their  fertility  is  much 
above  the  average.  All  these  things  indicate  a  certain  vital  exuberance, 
which  is  characteristic. 

The  great  majority  of  such  persons  whose  life-history  I  have  investi- 
gated, have  been  well  fed  and  well  housed,  having  had  nothing  to  do 
but  to  look  after  their  own  domestic  establishments.  They  have  usually 
enjoyed  excellent  health,  most  of  them  having  had  no  serious  illness 
since  youth,  rheumatic  fever  and  rheumatism  being  the  commonest 
diseases  from  which  they  have  suffered. 

In  short,  the  ensemble  of  facts  relative  to  the  life-history  of  cancer 
patients  shows,  that  they  have  almost  invariably  led  regular,  sober,  and 
industrious  lives.  Persons  of  drunken  and  dissolute  habits  are  com- 
paratively seldom  affected.  In  the  course  of  my  investigations  into  the 
life-history  of  female  cancer  patients,  I  have  been  much  struck  by  the 
extreme  rarity  with  which  signs  of  syphilis  etc.  are  met  with  in  such 
persons. 

Thus,  of  325  female  cancer  patients  consecutively  under  my  observa- 
tion, not  a  single  one  had  ever  been  addicted  to  prostitution,  so  far  as  I 
could  ascertain  ;  and,  what  is  still  more  remarkable,  only  a  single  one 
presented  undoubted  signs  of  having  had  syphilis. 

The  marked  fecundity  of  these  cancer  patients,  and  the  rarity  of 
sterility  and  abortion  among  them,  all  point  in  the  same  direction ;  for 
sterility  and  abortion  are  of  frequent  occurrence  in  prostitutes  and  the 
syphilitic. 

Considerations  of  this  kind  negative  the  doctrine  of  cancer  being 
morbus  miserice.  They  point  to  the  greater  prevalency  of  the  disease 
among  the  well-to-do  and  easy-going,  who  habitually  eat  more  than  is 
good  for  them.  Such  influences  as  are  comprised  under  the  terms 
"  alimentation  "  and  "  domestication,"  seem  to  me  to  be  of  paramount 
importance  in  the  aetiology  of  cancer. 


Scotland. 

For  the  last  half-century  the  Scotch  and  English  cancer  death-rates 
have  been  singularly  alike  ;  and  they  have  increased  pari  passu,  the  Scotch 
figures  generally  being  slightly  in  excess  of  their  English  counterparts  as 
follows  : 


1861  to  1870 

1871  „  1880 

1881  „  1890 

1891  „  1900 

1900 

1901 

1902 

1903 

1904 

1905 


Cancer  Death-rate 
per  Million  Living. 

..   416 

..  486 

..  578 

..  739 

..  800 

..  820 

..  830 

..  840 
.  850 


5—2 


68 


THE  NATURAL  HISTORY  OF  CANCER 


In  Scotland,  as  in  England,  the  increase  of  the  disease  has  affected 
both  sexes,  the  corresponding  death-rates  of  each  sex  in  the  two  countries, 
being  very  much  alike  ;  but  the  disproportionate  increase  among  males, 
is  less  marked  in  the  Scotch  than  in  the  English  returns.  The  Scotch 
figures  are  as  follows  : 


L     .. 


1881 
1885 
1890 
1895 
1900 

1 

lale  Cancer     ] 
Death-rate. 

390  .. 
420  .. 
470  .. 
560  .. 
640  .. 

"emale  Cancer 
Death-rate. 

630 
690 
740 

880 
950 

1901 
1902 
1903 
1904 
1905 

. 

670  .. 
660  .. 
690  .. 
680  .. 
700  .. 

970 
990 
970 
1020 
1070 

The  increase  of  cancer  in  Scotland,  has  been  accompanied  by  the  same 
concomitants  as  in  England — that  is  to  say,  by  diminution  of  the  mor- 
tality from  tubercle  and  zymotics,  decline  of  the  general  death-rate, 
progressive  population,  and  other  signs  of  material  prosperity  ;  while,  at 
the  same  time,  insanity,  suicide,  etc.,  have  increased. 

Thus,  the  tubercle  death-rate  declined  from  3,600  per  million  living 
in  1864,  to  2,300  in  1900,  and  to  2,070  in  1905.  In  like  manner,  the 
death-rate  from  phthisis,  which  was  2,220  in  1883,  fell  to  1,660  in  1900, 
and  to  1,460  in  1903,  and  these  declines  have  affected  both  sexes. 

As  in  England,  these  concomitants  have  coincided  with  urbanization, 
and  great  increase  of  material  prosperity. 

With  regard  to  the  former,  in  1801, 16-8  per  cent,  of  the  Scotch  popula- 
tion was  urban ;  in  1851  this  percentage  had  increased  to  26-9 ;  and  in 
1902  to  75-3.  The  environmental  change  has,  therefore,  been  almost  as 
complete  and  abrupt  as  in  England. 

With  regard  to  the  latter,  the  proportionate  increase  in  wealth  and 
wages  has  been  nearly  as  great  in  Scotland  as  in  England ;  and  it  has 
likewise  been  accompanied  by  abundance  of  food  and  improved  sanita- 
tion, whereby  the  depressing  and  disease-producing  tendencies  of  urban- 
ization have  been  combated. 

As  evidence  of  this,  the  decline  of  pauperism  may  be  instanced — viz., 
from  4-1  per  cent,  in  1869  to  2-3  per  cent,  in  1903. 

During  the  last  half-century  the  wealth  of  Scotland  has  enormously 
increased ;  and,  next  to  England,  Scotland  now  is  one  of  the  wealthiest 
countries  in  the  world,  the  average  wealth  per  inhabitant  having  been 
estimated  at  £260  by  Mulhall  in  1896,  as  against  £330  for  England. 

With  this  change,  the  dietary  habits  of  the  people  have  also  been 
radically  altered.  Porridge  is  no  longer  the  staple  food  as  formerly  ; 
meat  has  now  taken  its  place,  especially  in  the  towns.  Thus,  the  meat 
consumption  of  Scotland  in  1895,  has  been  estimated  at  180,000  tons  per 
annum ;  whereas  that  of  Ireland  only  amounted  to  80,000  tons,  although 
its  population  then  exceeded  that  of  Scotland. 

It  accords  with  the  foregoing,  that  cancer  is  found  to  be  least  prevalent 
in  the  islands  of  Scotland  (56  per  100,000  living  in  1900),  where  the 


THE  INCREASE  OF  CANCER,  AND  ITS  CONCOMITANTS    69 

people  are  poor  and  the  diet  is  mainly  vegetarian  ;  and  it  is  just  in  these 
localities,  notwithstanding  the  rural  conditions  of  existence,  that  phthisis 
is  most  prevalent  (182  per  100,000  living  in  1900). 

Similar  conditions  prevail  in  the  Shetland  Islands. 

With  regard  to  the  capital,  the  cancer  death-rate  of  Edinburgh  main- 
tains a  higher  average  than  that  for  any  other  town ;  and  the  rate  has 
increased  from  81  per  100,000  living  in  1881,  to  97  in  1891,  to  109  in  1901, 
and  to  135  in  1905  ;  while,  at  the  same  time,  the  tubercle  mortality  has 
declined,  the  death-rate  for  phthisis  now  being  very  low. 

In  the  principal  towns  similar  changes  have  taken  place.  Thus,  while 
the  cancer  death-rate  for  these  increased  from  70  per  100,000  living  in 
1891,  to  86  in  1902;  the  phthisis  death-rate  declined  from  218  in  the 
former  period,  to  161  in  the  latter. 

Among  the  large  towns,  Glasgow,  where  the  stress  of  life  is  con- 
siderable, has  long  been  remarkable  for  its  comparatively  low  average 
cancer  mortality,  coeval  with  a  high  death-rate  from  phthisis  ;  but  with 
the  improving  conditions  of  existence  for  the  masses  in  comparatively 
recent  times,  the  cancer  mortality  has  steadily  increased,  while  that 
from  phthisis  has  decreased.  Thus,  the  cancer  death-rate  has  augmented 
from  60  per  100,000  living  in  1891,  to  85  in  1902  ;  and  the  phthisis  mor- 
tality has  decreased  from  243  the  former  year,  to  177  in  the  latter. 

In  like  manner,  the  county  of  Berwick,  with  the  highest  cancer  death- 
rate  in  Scotland,  has  an  exceptionally  low  phthisis  mortality. 

Thus,  in  Scotland,  as  in  England,  it  is  evident  that  the  increasing 
incidence  of  cancer  goes  hand-in-hand  with  diminishing  incidence  of 
tuberculous  and  zymotic  maladies,  with  decline  of  the  general  mortality, 
progressive  population,  and  increased  material  prosperity,  of  which  the 
determining  factors  are  to  be  found  in  those  great  changes  wrought  in 
the  habits  and  mode  of  life  of  the  people,  by  industrialism  and  urbaniza- 
tion, as  I  have  previously  indicated. 


Ireland. 

The  vital  statistics  of  Ireland  during  the  last  sixty  years,  have  been 
so  perturbed  by  the  constant  diminution  of  population,  owing  to  emigra- 
tion en  masse,  with  the  consequent  reduction  in  numbers  by  nearly  one- 
half  ;  that,  in  their  crude  state,  they  are  only  available  in  a  certain  general 
way,  for  comparison  with  the  corresponding  English  and  Scotch  data, 
derived  from  progressive  populations,  which  have  nearly  doubled  their 
numbers  in  the  same  period.  In  consequence  of  this  disturbing  factor, 
the  Irish  population  contains  fewer  children  and  young  adults,  but  more 
elderly  persons,  especially  females,  than  either  the  English  or  Scotch 
populations,  and  its  average  age  is  much  higher.  The  resultant  effect  of 
these  perturbing  influences,  has  been  to  exaggerate  the  ostensible  cancer 
death-rate  of  Ireland,  as  compared  with  that  of  England  and  Scotland. 
Even  so,  however,  the  crude  cancer  death-rate  of  Ireland,  is  much  less 
than  that  of  either  of  the  sister  communities ;  and  during  the  last  half- 
century,  its  comparative  rate  of  increase  has  also  been  rather  less.  Thus, 


70  THE  NATURAL  HISTORY  OF  CANCER 

the  Irish  cancer  death-rate  increased  from  27  per  100,000  living  in  1864 
(when  registration  first  came  into  force),  to  61  in  1900,  to  65  in  1901,  to 
67  in  1903,  and  to  79-3  in  1906,  the  figures  for  intervening  years  being  33 
in  1870,  34  in  1880,  39  in  1885,  46  ir.  1890,  and  50  in  1895. 

The  highest  cancer  death-rate  is  found  in  well-to-do,  prosperous 
Armagh  (104) ;  and  the  lowest  in  poverty-stricken  Kerry  (26). 

In  Ireland,  as  in  England,  more  women  die  from  cancer  than  men, 
the  numbers  for  1906  being  1,566  males  and  1,915  females.  The  increase 
of  the  disease  has  likewise  affected  both  sexes,  but  with  undue  incidence 
on  males. 

Pauperism  and  insanity  are  more  prevalent  in  Ireland,  than  in  any 
other  division  of  the  United  Kingdom  ;  and  they  are  both  on  the  increase. 

The  prevalence  of  tubercle  in  Ireland,  moreover,  shows  no  such  ten- 
dency to  diminution  as  in  England.  Indeed,  the  mortality  from  this 
cause  slightly  increased  during  the  latter  part  of  the  nineteenth  century 
—viz.,  from  260  per  100,000  bring  in  1871-1880,  to  290  in  1897-1900  ;  and 
it  is  the  same  with  regard  to  phthisis,  the  death-rate  having  increased 
from  192  in  1871,  to  203  in  1906,  after  having  been  stationary  for  several 
years. 

Although  Ireland  is  a  very  much  poorer  country  than  England,  and 
although  its  material  prosperity  has,  during  the  last  half-century,  aug- 
mented much  more  slowly  than  that  of  England ;  yet,  as  Dr.  Grimshaw 
has  shown,1  its  aggregate  wealth  has  steadily  increased,  notwithstanding 
the  decrease  of  population  and  the  poverty  of  the  bulk  of  the  people. 
This  result  is  mainly  due  to  the  growth  of  manufacturing  and  industrial 
enterprises  in  a  few  localities — e.g.,  in  Ulster,  in  Dublin  and  its  vicinity, 
and  in  Carlow,  for  which  the  community  is  mainly  indebted  to  persons 
of  Anglo-Scotch  descent,  who  are  numerous  in  these  localities.  Now,  it 
is  just  in  these  places  that  the  highest  cancer  death-rates  are  found.  For 
instance,  Ulster,  the  seat  of  the  great  linen  and  other  industries,  had  a 
cancer  death-rate  of  77  in  1901,  which  is  much  above  the  average  ;  while 
its  phthisis  death-rate  was  210. 

Moreover,  it  is  mainly  owing  to  augmentation  of  the  disease  in  these 
localities,  that  the  increased  cancer  mortality  of  Ireland,  as  a  whole,  is  due. 

In  almost  all  other  parts  of  Ireland,  where  rural  conditions  of  exist- 
ence prevail,  and  the  bulk  of  the  people  are  decidedly  poor  and  ill-fed, 
as  compared  with  their  English  compatriots,  cancer  is  comparatively 
rare,  while  tubercle  is  very  prevalent. 

Switzerland. 

There  are  no  official  statistics  relating  to  the  causes  of  death  for  the 
whole  country ;  but,  according  to  Nencki's  research,2  which  is  based  on 
the  cantonal  reports,  cancer  is  more  prevalent  in  Switzerland  than  in 
any  other  country,  the  death-rate  from  this  cause  having  augmented 
from  114  in  1889,  to  132  per  100,000  living  in  1898.  This  high  cancer 

2  £eP°rt  of  tne  Commission  on  the  Financial  Relations  of  England  and  Ireland,  1894. 
"  Die  Frequenz  und  Verteilung  des  Krebses  in  der  Schweiz,"  etc      Z°its    f    schw 
Statistik,  1900,  vol.  ii.,  p.  332. 


THE  INCREASE  OF  CANCER,  AND  ITS  CONCOMITANTS      71 

mortality  is  associated  with  the  comparatively  low  phthisis  death-rate 
of  189. 

During  the  same  period  tubercle  has  steadily  declined,  the  phthisis 
death-rate  having  fallen  from  234  in  1876-1880,  to  187  in  1901. 

Three-fourths  of  Switzerland  is  mountainous,  comprising  large  areas 
of  forests.  The  proportion  of  town-dwellers  is  a  quarter,  and  it  is  in- 
creasing. Of  its  1,500,000  workers,  two-thirds  are  engaged  in  industrial 
and  commercial  occupations,  and  only  one-third  in  agriculture. 

About  two-thirds  of  the  people  are  of  German  descent,  the  remainder 
being  of  French  and  Italian  origin. 

Half  a  century  ago,  Switzerland  was  an  exceedingly  poor  country ; 
now  it  is  one  of  the  most  prosperous  and  well-to-do  communities  in 
Europe,  the  average  wealth  per  inhabitant  being  £165,  or  £8  more  than 
in  Germany  (Mulhall). 

There  are  no  millionaires  in  Switzerland,  and  no  paupers ;  so  that 
prosperity  is  even  more  widely  diffused  than  in  France. 

The  population  has  been  steadily  progressive,  with  a  diminishing 
general  death-rate  ;  and  the  meat  consumption  is  considerable  (85  pounds 
per  head  per  year  in  1895). 

The  cancer  mortality  varies  greatly  in  the  different  cantons — viz., 
from  204  per  100,000  living  in  wealthy  Lucerne,  to  36  in  poverty-stricken 
Valais. 

Denmark. 

Next  to  Switzerland,  Denmark  is  reputed  to  have  the  highest  cancer 
death-rate  of  any  country  in  Europe — viz.,  130  per  100,000  living  in  1900  ; 
but  statistical  data  are  available  only  for  the  towns,  the  inhabitants  of 
which  comprise  but  a  quarter  of  the  entire  population ;  so  that  the  figure 
for  the  whole  country,  although  high,  wrould  be  considerably  less  than 
the  above. 

In  these  same  towns,  with  this  high  cancer  mortality,  we  find  asso- 
ciated the  very  low  phthisis  death-rate  of  150. 

In  1886-1887  the  cancer  death-rate  of  the  Danish  towns  was  109,  so 
that  considerable  increase  has  since  taken  place.  During  the  same  period 
the  incidence  of  phthisis  has  markedly  declined — viz.,  from  about  300- 
in  1870-1874,  to  150  in  1900. 

Denmark  is  an  agricultural  country  whose  population,  notwith- 
standing the  absence  of  any  great  development  of  manufacturing  in- 
dustries, has  nevertheless  in  a  comparatively  brief  period,  experienced  a 
sudden  change  from  serfdom  and  poverty,  to  freedom  and  great  pros- 
perity. Serfdom  was  only  abolished  at  the  end  of  the  eighteenth  cen- 
tury ;  and  since  then  these  emancipated  serfs  have  largely  become  yeomen 
proprietors  of  their  small  holdings;  so  that,  in  1890,  71,000  peasant 
proprietors  owned  four-fifths  of  the  total  soil.  Their  present  state  of 
prosperity  is  well  indicated  by  the  fact  that :  "the  ratio  of  wealth  per 
head  of  the  population  is  now  higher  than  in  any  other  country  of  Con- 
tinental Europe,  except  France  "  (Mulhall). 

The  only  large  city  in  Denmark  is  Copenhagen,  wThose  inhabitants 
total  one-sixth  of  the  entire  population. 


72  THE  NATURAL  HISTORY  OP  CANCER 

The  cultivated  area  is  proportionally  larger  than  that  of  other  European 
countries,  and  there  are  but  few  forests. 

Denmark  produces  hardly  any  coal  or  minerals,  so  that  manufacturing 
industries  are  much  less  dominant  than  in  most  modern  communities. 

France. 

In  dealing  with  French  vital  statistics,  due  allowance  must  be  made 
for  the  fact  that  they  relate  only  to  the  towns,  which  comprise  a  popula- 
tion of  about  12,000,000  out  of  a  total  of  nearly  39,000,000. 

These  data  show  that  cancer1  is  very  prevalent,  and  that  the  incidence 
of  the  malady  is  increasing. 

For  Paris,  the  following  figures2  indicate  the  cancer  death-rates  : 
1865,  84  ;  1870,  91  ;  1880,  94  ;  1890,  108  ;  and  1900,  120. 

For  all  towns  of  above  10,000  inhabitants  (omitting  Paris),  the  figures 
are  :  1887,  76  ;  1890,  91  ;  1895,  100  ;  and  1900,  106. 

The  lowest  cancer  death-rates  are  found  along  the  Mediterranean 
littoral  (Corsica,  32  etc.)  and  in  Brittany  (Finisterre,  38),  where  the 
people  are  comparatively  poor  ;  and  the  highest  are  in  prosperous  Nor- 
mandy and  the  adjacent  departments  (Rouen,  173  ;  Eure-et-Loire,  167 
etc.). 

The  French  population,  although  still  predominantly  rural,  has  under- 
gone much  urbanization,  the  ratio  of  urban  to  rural  inhabitants  having 
increased  from  24  in  1846  to  43  in  1900;  and  this  change  is  almost  entirely 
due  to  the  disproportionate  growth  of  the  large  towns — e.g.,  Paris,  Lyons, 
Marseilles,  Lille,  Bordeaux  etc. 

The  tubercle  mortality  of  the  towns  is  high ;  and  although  Paris  (439 
in  1887,  to  394  in  1901),  and  some  of  the  largest  cities,  show  improvement 
in  this  respect,  in  other  towns  the  decline  is  but  slight.  The  phthisis 
mortality  for  all  the  towns,  which  was  245  in  1877,  had  declined  to  213 
in  1903. 

Next  to  England,  France  is  the  richest  country  in  Europe,  and  its 
wealth  has  been  steadily  increasing  throughout  the  last  century  ;  but 
the  wealth  of  France  is  much  more  widely  diffused  than  that  of  England. 
Thus,  while  the  working  classes  in  the  two  countries  number  about  the 
same,  the  French  workers  own  4,330  millions  worth  of  property,  against 
only  566  for  their  English  compeers.  The  riches  of  France  are,  as  it 
were,  clotted  in  the  large  towns  ;  and  these,  as  I  have  previously  indicated, 
everywhere  have  a  higher  cancer  mortality  than  the  small  towns,  chefs- 
lieux  d'arrondissement  etc. 

Sweden. 

As  in  other  Scandinavian  countries,  the  cancer  mortality  of  Sweden 
is  high.     Statistics  exist  only  for  the  towns,  of  which  but  two  (Stock- 
holm and  Gottenburg)   contain  more  than   100,000   inhabitants.     The 
urban  population  comprises  about  one-fifth  of  the  total  inhabitants. 
"  Cancer  et  autres  tumeurs." 

2  For  these  data  I  am  indebted  to  Dr.  J.  Bertillon  ;  see  also  his  annual  publications 
in  the  "  Annuaire  Statistique  de  la  ville  de  Paris,"  and  for  the  other  towns  the  "  Annuaire 
Statistique  Sanitaire  des  villes  de  France,"  etc. 


THE  INCREASE  OF  CANCER,  AND  ITS  CONCOMITANTS     73 

Judged  by  death-rates,  the  Swedes  are  one  of  the  healthiest  races  in 
the  world,  for  their  general  death-rate  during  the  last  decade  was  only 
16-4,  the  corresponding  figures  for  Norway  and  England,  the  next  best 
on  the  list,  being  16-9  and  18-8  respectively. 

According  to  Quensel,  there  was  progressive  increase  in  the  mortality 
from  cancer  during  the  last  quarter  of  the  nineteenth  century — viz.,  from 
80  per  100,000  inhabitants  in  1875-1879,  to  97  in  1895-1899.  In  the 
former  period  the  deaths  from  cancer  amounted  to  3-37  of  the  total 
mortality  ;  in  the  latter  to  6-27.  In  1900,  the  cancer  death-rate  had 
increased  to  102.  To  this  increase  men  have  contributed  more  than 
women,  the  sex  ratios,  which  in  1875-1879  were  100  males  to  192  females, 
having  changed  to  100  to  150  in  1895-1899. 

Tubercle  is  very  much  less  prevalent  in  Sweden  than  in  most  European 
countries,  and  the  mortality  from  this  cause  has  declined.  Thus,  the 
phthisis  death-rate  for  the  towns,  which  was  280  in  1886-1887,  in  1900 
had  fallen  to  170. 

A  curious  feature  revealed  by  Quensel's  research  is,  that  the  cancer 
death-rate  of  the  small  towns  exceeded  that  of  the  large  ones.  Thus, 
the  rate  for  communities  of  less  than  2,000  inhabitants  was  100  ;  for 
those  of  from  2,000  to  10,000,  90  ;  and  for  those  of  over  10,000  inhabi- 
tants, 85. 

As  previously  mentioned,  this  anomaly,  taken  with  other  similar 
indications,  seems  to  show  that  the  incidence  of  cancer  is  determined 
more  by  local  conditions  of  existence,  than  it  is  by  urban  or  rural  life 
per  se. 

The  average  consumption  of  flesh  food  per  head  per  year  is  only 
67  pounds  (Mulhall)  ;  but  the  Scandinavians  rely  for  their  proteids  quite 
as  much  on  milk,  cheese,  and  fish,  of  which  immense  quantities  are  con- 
sumed, as  they  do  on  meat.  From  what  I  have  myself  seen  of  the  dietetic 
habits  of  the  Scandinavians,  I  have  come  to  the  conclusion  that  their 
consumption  of  proteids  exceeds  that  of  most  European  nations. 

Norway. 

In  Norway,  the  population  is  even  more  predominantly  rural  than  in 
Sweden ;  and,  besides  agriculture,  the  lumber  trade,  fishing,  commerce, 
and  cattle-rearing,  are  their  chief  resources. 

The  Norwegian  statistics,  unlike  those  of  Sweden,  apply  to  the  whole 
population  ;  and  they  show  steady  increase  in  the  cancer  mortality.  Thus, 
in  1880,  the  rate  was  43  ;  in  1890,  61  ;  and  in  1900,  92.  The  tubercle 
mortality  is  almost  as  low  as  that  of  Sweden.  The  highest  cancer  mor- 
tality is  met  with  in  the  centres  of  the  fishing,  shipping,  and  timber 
industries,  where  the  people  are  financially  the  most  prosperous. 

Holland. 

This  country,  which  consists  of  a  fertile  alluvial  plain  traversed  by 
rivers  and  canals,  is  noted  for  its  prosperity,  which  is  largely  due  to 
agriculture.  The  cancer  mortality  is  high  and  increasing.  In  1867-1879 


74  THE  NATURAL  HISTORY  OF  CANCER 

the  cancer  death-rate  was  49  ;  in  1884-1888,  66  ;  in  1890,  79  ;  in  1900,  93  ; 
in  1903,  99  ;  and  in  1905,  101.  Its  tubercle  mortality  is  decidedly  low — 
viz.,  about  180 — while  in  1903  the  death-rate  from  phthisis  was  only  132, 
and  both  are  declining. 

The  lowest  cancer  death-rate  (77)  is  in  the  comparatively  poor  and 
unproductive  province' of  Drenthe,  where  large  pauper  colonies  have  been 
established. 

In  Amsterdam,  the  cancer  mortality  increased  from  38  in  1891,  to 
78  in  1900  ;  while  the  death-rate  from  phthisis  fell  from  260  in  1862-1863, 
to  177  in  1897-1901. 

Germany. 

According  to  Maeder  *  and  Wutzdorff,2  whose  researches  are  based 
upon  official  data,3  cancer  has  of  late  increased  in  Germany,  while  tubercle 
has  declined ;  and  these  changes  have  coincided  with  increased  general 
prosperity. 

The  cancer  death-rate,  which  was  59  in  1872,  increased  to  71  in 
1900.  Per  contra,  the  tubercle  mortality  has  declined  38  per  cent,  since 
1875. 

In  Berlin,  the  cancer  rate  increased  from  57  in  1870-1882,  to  109  in 
1899  ;  while  phthisis  declined  from  310  in  1876,  to  190  in  1901. 

The  Hamburg  cancer  rate  increased  from  71  in  1872,  to  97  in  1898. 
During  the  same  period,  the  mortality  from  phthisis  declined  from  340 
in  the  former  year  to  194,  in  the  latter  ;  and  there  was  also  marked  dimi- 
nution in  the  general  death-rate. 

Of  the  constituent  States  of  Germany,  the  rich  southern  ones  have 
much  the  highest  cancer  death-rates. 

Baden  heads  the  list  (101),  and,  as  Maeder  has  shown,  the  disease  has 
increased  there. 

Bavaria  comes  next,  with  an  increase  from  56  in  1880,  to  98  in  1900. 
In  Munich  the  increase  was  from  88  in  1890,  to  119  in  1900. 

In  Saxony,  the  increase  has  been  from  69  in  1876-1885,  to  95  in  1900. 
During  about  the  same  period  phthisis  declined  from  231  (1873-1875), 
to  190.  Of  late,  the  high  Dresden  cancer  rate  has  been  about  stationary 
—viz.,  123  in  1891,  and  125  in  1900. 

In  Stuttgart,  the  cancer  death-rate  increased  from  76  in  1891,  to  127 
in  1900. 

The  average  cancer  mortality  in  Prussia  is  much  less  than  that  of 
these  southern  States,  but  even  here  the  disease  has  increased — viz., 
from  31  in  1881,  to  59  in  1900,  and  to  60  in  1905.  The  phthisis  death- 
rate  has  declined  from  360  in  1851,  to  150  in  1901  ;  but  insanity  has 
notably  increased. 

Cancer  is  probably  more  prevalent  in  Schleswig-Holstein  (76),  where 
Danish  conditions  of  existence  prevail,  than  in  any  other  division  of 
Prussia;  and  the  Kiel  rate  (113),  is  higher  than  that  of  any  Prussian 
town. 

1  Zeits.  f.  Hygiene,  etc.,  Bd.  xxxiii.,  1900,  S.  235. 

2  Deutsche  med.  Woch.,  March  6,  1902. 

3  "  Medizinal-Stat.  Mittheil.,  aus  den  k.  Gesundheitsamte." 


THE  INCREASE  OF  CANCER,  AND  ITS  CONCOMITANTS      75 

It  is  least  prevalent  in  the  provinces  bordering  on  Poland — Posen  (44), 
East  Prussia  (54),  West  Prussia  (50),  and  Silesia  (54) — where  the  working 
classes  are  poor,  comprising  many  Poles  and  Jews. 


Austria. 

In  this  country  the  cancer  mortality  has  increased  from  37  in  1880. 
to  70  in  1900 ;  and  coincidently  there  has  been  a  great  decline  in  the 
death-rates  from  phthisis  and  all  kinds  of  tuberculosis.  The  tubercle 
rate  is,  however,  still  high — viz.,  349  for  phthisis  in  1903. 

The  highest  cancer  death-rates  are  met  with  in  the  prosperous  and 
well-to-do  provinces  of  Salzburg  (133),  Upper  Austria  (115),  Lower 
Austria  (108),  Tyrol  and  Vorarlberg  (107)  etc.  ;  and  the  lowest  in  the 
poor  provinces  of  Bukowina  (37),  Galicia  (28),  and  Dalmatia  (19).  In 
Bukowina  and  Galicia,  Polish  Jews  comprise  a  large  proportion  of  the 
population,  and  in  Dalmatia  there  is  a  large  Italian  element. 

In  Vienna  the  cancer  rate  increased  from  107  in  1875,  to  121  in  1900. 
With  regard  to  tubercle,  the  mortality  declined  from  763  in  1872-1876, 
to  467  in  1897-1900. 


Hungary. 

As  compared  with  Austria,  Hungary  is  a  poor  country,  with  the 
phenomenally  low  cancer  death-rate  of  33,  which  in  1897  was  only  26, 
and  in  1903  it  reached  39.  The  tubercle  mortality  of  Hungary  is  the 
highest  in  Europe — viz.,  387  in  1903. 

The  Buda-Pest  cancer  rate  increased  from  62  in  1896,  to  72  in  1900, 
and  the  tubercle  mortality  has  declined  of  late. 


Italy. 

Cancer  is  much  less  prevalent  in  Italy,  which  is  a  comparatively  poor 
country,  than  in  most  European  communities  ;  but  even  here  the  mor- 
tality has  increased  from  21  in  1880,  to  52  in  1899,  and  to  58  in  1905. 

The  tubercle  death-rate  is  diminishing,  but  to  a  less  extent  than  in 
most  European  countries,  having  fallen  from  122  in  the  period  1897- 
1904,  to  118  in  1905. 

The  meat  consumption  per  head  (23  pounds  in  1895)  is  the  smallest 
of  any  European  nation. 

The  highest  cancer  rates  are  met  with  in  the  prosperous  and  well- 
to-do  provinces  of  the  north — Tuscany  (83),  Emilia  (78),  Lombardy  (71) 
etc. — and  it  is  here  that  the  diminution  in  the  tubercle  mortality  has 
been  most  marked.  The  lowest  cancer  rates  are  in  the  comparatively 
poor  provinces  of  Apulia,  Basilicata,  and  Calabria  (30),  while  for  Sardinia 
the  phenomenally  low  rate  of  19  is  registered. 

For  the  chief  towns  the  cancer  rates  are  as  follows  :  Florence,  137  ; 
Ravenna,  120  ;  Milan,  101  ;  Venice,  103  ;  Rome,  77  ;  Turin  and  Genoa,  59  ; 
and  Naples,  56. 


76  THE  NATUKAL  HISTORY  OF  CANCER 


United  States. 

With  regard  to  extra-European  countries,  data  are  available  for  the 
United  States,  Australia,  and  New  Zealand. 

In  what  follows  in  this  section  the  reservation  previously  made,  with 
regard  to  the  peculiar  difficulties  under  which  vital  statistics  are  com- 
piled in  the  United  States,  must  be  borne  in  mind. 

Such  data  as  are  forthcoming  for  the  whole  community  show  that 
the  mortality  from  cancer  and  tumour  increased  from  9  per  100,000  living 
in  1850,  to  29  in  1880,  to  33  in  1890,  and  to  43  in  1900.  The  proportion 
of  deaths  from  this  cause  to  1,000  deaths  from  all  causes,  increased  from 
25-4  in  1890,  to  32-9  in  1900. 

In  the  "registration  area"  alone,  the  "cancer  and  tumour"  death- 
rate  increased  from  53  in  1890,  to  65  in  1900. 

In  the  same  limited  area,  the  death-rate  from  cancer  alone,  increased 
from  47  in  1890,  to  60  in  1900. 

There  is  no  need  to  dilate  upon  the  great  increase  in  the  riches, 
prosperity,  and  population  of  the  United  States  during  the  nineteenth 
century,  although  it  may  here  be  remarked  that,  as  in  England,  the 
wealth  of  the  community  is  much  less  widely  diffused  among  the 
population  than  in  France,  Switzerland,  Denmark,  and  some  other 
countries. 

Although  urbanization  has  made  great  progress  in  the  United  States, 
the  towns  of  8,000  inhabitants  and  upwards  having  increased  from  6  in 
1790,  to  546  in  1900,  nevertheless,  two-thirds  of  the  population  still  dwell 
in  the  country,  and  are  mainly  dependent  upon  agriculture. 

A  diminishing  tubercle  death-rate  has  coincided  with  the  increase  of 
cancer,  the  tubercle  rate  having  fallen  from  245  in  1890,  to  187  in 
1900. 

The  meat  consumption  of  the  United  States  population,  is  consider- 
ably in  excess  of  the  European  average. 

Cancer  is  much  more  prevalent  in  the  northern  than  in  the  southern 
part  of  the  United  States,  the  chief  centres  being  the  wealthy  commercial 
States  of  the  Atlantic  coast"  and  vicinity  (51  to  41)  and  the  Pacific  States 
(51).  The  lowest  rates  are  in  the  South  Mississippi  River  belt  (11),  the 
south-west  central  region'  (15),  the  southern  interior  plateau  (18)  etc. 
It  is  in  these  southern  localities  that  the  negro  race  is  chiefly  comprised ; 
and  their  cancer  death-rate  (47)  is  lower  than  that  of  the  whites  (66) ;  but, 
even  in  southern  States  where  negroes  are  rarely  found,  the  cancer  rates 
are  very  much  below  the  average. 

For  some  of  the  chief  cities  of  the  United  States,  the  following  increases 
in  the  cancer  death-rates  have  been  recorded  :  New  York,  from  32  (1864) 
to  67  (1900)  ;  Chicago,  from  32  (1880)  to  63  (1900)  ;  Philadelphia,  from 
31  (1861)  to  70  (1904)  ;  Boston,  from  28  (1863)  to  85  (1903)  ;  Baltimore, 
from  18  (1864)  to  63  (1903)  ;  New  Orleans,  from  15  (1864)  to  82  (1903)  ; 
and  San  Francisco,  from  16  (1866)  to  112  (1900). 


THE  INCREASE  OF  CANCER,  AND  ITS  CONCOMITANTS     77 


Australia. 

Thanks  to  the  valuable  publications  of  Adams,1  Allen,2  Mullins,8 
Coghlan,4  etc.,  we  have  fairly  complete  information  as  to  the  incidence 
of  cancer  in  Australia  during  the  last  half-century.  These  data  show 
steady  increase  of  the  disease,  the  death-rate  per  100,000  living  having 
been  as  follows  :  14  (1851),  19  (1861),  25  (1871),  32  (1881),  45  (1891), 
and  57  (1901). 

Males  have  been  relatively  affected  by  this  increase  more  than  females. 
Thus,  during  the  period  1870-1900,  the  male  rate  increased  from  26 
to  59,  whereas  the  augmentation  for  females  was  from  28  to  55  (Allen). 
A  remarkable  fact  revealed  by  these  data  is,  that  the  male  cancer  death- 
rate  now  exceeds  the  female  rate  ;  and  this  holds  as  well  for  each  of  the 
constituent  communities,  as  for  the  whole  commonwealth. 

Some  conception  may  be  formed,  as  to  the  conditions  of  existence 
during  the  period  to  which  these  data  refer,  from  the  fact  that  it  has  been 
characterized  by  great  increase  and  wide  diffusion  of  material  prosperity, 
by  diminution  of  the  tubercle  and  general  mortality,  by  increase  of 
insanity,  by  lessened  birth-rate,  by  excessive  consumption  of  meat,  and 
by  disproportionate  increase  of  the  capital  towns. 

For  the  different  divisions  of  the  Australian  Commonwealth,  the  fol- 
lowing progressive  increases  in  the  cancer  rates  have  been  recorded  : 

New  South  Wales  :  28  (1871-1875),  51  (1894),  57  (1900),  and  65  (1903). 
For  males,  the  rate  increased  from  18  (1860-1864)  to  51  (1895-1899) ;  and, 
for  females,  from  21  (1860-1864)  to  50  (1895-1899). 

The  phthisis  death-rate  declined  from  92  (1871-1875)  to  79  (1896- 
1898). 

Victoria  :  32  (1871-1875),  61  (1891-1895),  72  (1900),  and  76  (1903). 

The  phthisis  rate  was  120  (1871-1875),  123  (1896-1898),  and  111  (1903). 

Queensland :  17  (1871-1875),  35  (1891-1895),  46  (1900),  and  49  (1903). 

The  phthisis  rate  declined  from  109  (1871-1875)  to  93  (1896-1908), 
and  to  78  (1903). 

South  Australia  :  20  (1871-1875),  47  (1891-1895),  59  (1900),  and  72 
(1903). 

The  phthisis  rate  was  89  (1871-1875),  87  (1896-1898),  and  75  (1905). 

West  Australia  :  15  (1871-1875),  30  (1891-1895),  32  (1898),  and  40 
(1905). 

The  phthisis  rate  declined  from  85  (1871-1875)  to  75  (1896-1898),  and 
to  65  (1905). 

Tasmania  :  48  (1871-1875),  49  (1891-1895),  60  (1900). 

The  phthisis  rate  declined  from  101  (1871-1875)  to  73  (1896-1898). 

While  the  average  cancer  death-rate  for  all  Australia  was  57  in  1900, 
or  5  per  cent,  of  the  total  mortality  from  all  causes,  in  the  capital  cities 
the  cancer  death-rate  was  81,  or  6-4  per  cent,  of  the  total  mortality  ; 

1  Lancet,  1904,  vol.  i.,  pp.  423,  498. 

2  Australian  Medical  Gazette,  April  21,  1902,  p.  169. 

3  Ibid.,  January  20,  1896. 

4  Ibid.,  April  21,  1902,  p.  174  ;  eee  also  his  "  Wealth  and  Progress  of  New  South 
Wales,"  1894. 


78  THE  NATURAL  HISTORY  OF  CANCER 

whereas,  in  the  rural  districts,  the  cancer  rate  was  only  44,  or  3-9  per 
cent,  of  the  total  deaths  from  all  causes. 

I  have  previously  referred  to  the  greatly  increased  proclivity  to 
cancer  experienced  by  British  immigrants  in  Australia,  of  which  the 
latest  Australian  vital  statistics  afford  some  striking  evidence.  Thus, 
for  1900,  while  the  cancer  death-rate  of  native-born  Australians  was  only 
22,  the  corresponding  rate  for  the  British-born  was  203  ;  and,  for  other 
foreign-born  persons,  as  follows  :  French,  375  ;  Austrian,  300  ;  Scandi- 
navian, 289  ;  and  German,  252.  In  1895,  Mullins  found  that  of  the 
British-born,  in  Australia,  1  in  966  died  of  cancer,  as  against  1  in  7,746  of 
the  native-born  white  Australians.  These  rates  are  much  in  excess  of 
those  prevalent  in  the  immigrants'  native  countries. 

Even  when  the  figures  have  been  corrected  for  age  differences,  the 
same  result  is  shown ;  for,  taking  persons  aged  thirty-five  years  and 
upwards,  58  per  100,000  living  of  the  Australian-born  died  of  cancer,  as 
against  137  of  the  British  and  foreign-born. 

Dr.  MacDonald,  of  Dunedin,  believes  that  this  proclivity  is  mainly 
due  to  the  gluttonous  habits  of  the  immigrants  in  respect  to  meat- 
eating  :  "  Meat  for  breakfast,  lunch,  dinner,  tea,  and  supper,  just  like 
the  porridge-pot  in  Scotland." 

Even  the  Chinese  in  Australia  suffer  severely  from  cancer,  for  their 
mortality  from  this  cause,  in  1900,  amounted  to  72  per  100,000  ;  and  of 
1,316  Chinese  deaths  registered  in  Victoria  in  1894-1900,  42  were  due  to 
this  malady. 

With  regard  to  the  Australian  aborigines,  however,  who  in  1891 
numbered  about  60,000,  Allen  notes :  that  "  cancer  is  rare  among  them, 
many  years  often  passing  without  a  single  case  being  registered,  although 
they  are  not  really  exempt  from  either  external  or  internal  cancer." 

Among  the  Pacific  Islanders,  employed  in  Queensland,  Roth  reports 
that,  during  the  last  eleven  years,  he  has  never  seen  or  heard  of  a  single 
case  of  cancer  ;  and  several  other  medical  men  have  testified  to  the  same 
effect. 

New  Zealand. 

In  these  islands  the  conditions  of  existence  much  resemble  those 
current  in  Australia ;  and  the  proclivity  to  cancer  is  much  the  same  in 
the  two  countries,  the  New  Zealand  rate  having  increased  from  32  (1877- 
1888),  to  44  (1891),  to  60  (1900),  and  to  71  (1903).  Taking  100  as  the 
standard,  the  cancer  mortality  for  males  in  the  last  twenty  years  increased 
to  367,  as  against  260  for  females.  The  phthisis  rate  declined  from  87 
(1871-1875),  to  75  (1900),  and  to  69  (1903).  In  New  Zealand,  as  in 
Australia,  the  birth-rate  and  the  general  mortality  have  declined,  while 
insanity  has  increased.  British  immigrants  are  much  more  prone  to 
cancer,  than  the  native-born  white  New  Zealander ;  but,  the  aborigines 
are  seldom  affected. 


CHAPTER  IV 
THE  TOPOGRAPHICAL  DISTRIBUTION  OF  CANCER 

IN  every  part  of  the  world  the  incidence  of  cancer  presents  well-marked 
topographical  variations,  to  many  of  which  I  have  referred  in  the  fore- 
going chapters  ;  but  the  importance  of  the  subject  seems  to  demand 
more  detailed  consideration. 

C.  H.  Moore1  was  the  first  to  study  these  variations  for  England  and 
Wales.  He  showed  that  the  disease  was  more  prevalent  in  London  and 
its  vicinity,  in  the  southern  and  eastern  counties,  than  elsewhere ;  and 
that  it  was  least  prevalent  in  the  north-western  and  northern  counties, 
and  in  Wales.  If,  he  says,  the  country  be  divided  by  a  line  drawn  from 
Bristol  to  Peterborough,  the  mortality  from  cancer  in  the  southern 
divisions  is  considerably  in  excess  of  that  on  the  north  of  the  line.  In 
the  year  1861,  for  instance,  one  of  every  thirty  deaths  of  females  in  the 
south-eastern  division  was  due  to  cancer ;  while  in  the  north-western 
division,  the  proportion  was  only  1  to  59,  or  about  one-half.  Moore 
gives  the  following  instructive  data  (see  table,  p.  80). 

Some  years  later  the  same  subject  was  thoroughly  reinvestigated, 
with  due  allowance  for  diversities  in  age  and  sex  distribution,  by  Havi- 
land,2  and  Moore's  results  were  in  every  respect  confirmed. 

The  districts  having  the  highest  cancer  mortality  (4  to  6  per  10,000 
living)  comprised  London,  the  south-eastern  and  eastern  counties ; 
those  with  the  lowest  mortality  (3  to  under  2  per  10,000  living) 
were  the  north-western  counties,  Monmouth,  and  Wales ;  between  these 
extremes  were  the  northern,  midland,  and  south-western  counties,  with 
a  cancer  death-rate  of  from  3  to  4  per  10,000  living. 

These  investigations  comprised  the  decennia  1851-1860  and  1861- 
1870 ;  and,  although  in  the  intervening  period,  the  cancer  mortality 
was  shown  to  have  everywhere  increased,  yet  those  localities  having 
the  highest,  lowest,  and  medium  cancer  rates  were  the  same  for 
both  periods. 

In  the  Forty-seventh  Annual  Report  of  the  Registrar-General,  this 
subject  received  official  attention.  The  subjoined  table  (see  p.  81)  from 
this  source,  shows  the  mean  annual  cancer  mortality  per  standard  million 

1  "  Antecedents  of  Cancer,"  London,  1865,  p.  41. 

2  "  Geographical  Distribution  of  Disease  in  Great  Britain,"  2nd  edit.,  1892 ;  1st  edit., 

1875. 

79 


80 


THE  NATURAL  HISTORY  OF  CANCER 


1851. 

1861. 

1851-1860. 

One  Cancer 
Death  to 

One    to 
Total 

One  Cancer 
Death  to 

One  to 
Total 

One 

Death    ! 

One  Death 
from  Can- 

Divisions. 

Population. 

Deaths. 

Population. 

Deaths. 

from 
Cancer 

cer  in 
Total  Fe- 

i 

Female. 

I 

i 

1 

i 

Female. 

in  Fe- 
males 
aged  35 
to  64. 

male  Mor- 
tality 
between 
Ages  35 
to  64. 

London 

4884 

1778 

113 

38 

3758 

1553 

95 

34 

67 

12 

S.  -Eastern  :      ^ 

(Surrey,  Kent,    1 
Sussex,  Hamp-   j 
shire,  Berkshire  )) 

5362 

2206 

105 

41 

4419 

1697 

86 

30 

83 

12 

South-Midland:  A 

(Middlesex, 

Herts,  Bucks, 

Oxfordshire, 
Northampton, 

4304 

2163 

87 

42 

3520 

2141 

72 

41 

89 

13 

Huntingdon- 

shire,   Beds, 

Cambridgeshire)  _ 

Eastern  :        ^1 

(Essex,  Sussex,   J- 
Norfolk)        J 

7226 

2131 

150 

42 

4553 

1713 

98 

34 

84 

12 

S.-Western  :     ^ 
(Wilts,  Dorset,   1 
Devon,  Somer-   j 
set,  CornwaU)  J 

4921 

2343 

103 

45 

4309 

1920 

85 

34 

100 

14 

W.-Midland:    ^ 

(Gloucestershire, 

Herefordshire, 

Shropshire,  Staf- 

7478 

2470 

177 

55 

5057 

2175 

109 

42 

90 

u 

fordshire, 

Worcestershire, 

Warwickshire)  , 

N.-Midland  :     * 

(Leicestershire, 

Rutland,  Lines, 

6417 

2692 

131 

54 

4499 

2329 

96 

47 

97 

14 

Notts,  Derby- 

shire) 

N.-Western  : 

(Lancashire, 

7946 

3263 

214 

80 

6249 

2454 

166 

59 

103 

20 

Cheshire) 

Yorkshire  : 

(West,  East, 
and  North 

5881 

2869 

141 

65 

4634 

3068 

110 

45 

100 

16 

Ridings) 

Northern  : 

(Durham, 

Northumber- 
land, Cumber- 

5454 

2970 

119 

60 

3983 

2258 

92 

49 

102 

16 

land,  West- 

morland) 

Wales  :         ^ 

(North,  South,    1 
and  Mon-        j 

7166 

3833 

149 

74 

4282 

2962 

92 

59 

137 

20 

mouthshire)     J 

England  and    "I 
Wales          / 

5846 

2461 

133 

52 

4484 

2019 

101 

41 

91 

15 

THE  TOPOGRAPHICAL  DISTRIBUTION  OF  CANCER       81 


aged  twenty-five  and  upwards,  in  the  registration  divisions  during  the 
thirty  years  1851-1880  : 


'     1 

Males. 

Females. 

Persona. 

London 

736 

1463 

1117 

South-Eastern    .            .              ... 

557 

1207 

898 

South-Midland   .            .              ... 

597 

1148 

886 

Eastern 

502 

1175 

855 

West-Midland     

519 

1133 

841 

Yorkshire            

511 

1114 

827 

Northern             .            .              ... 

565 

1041 

815 

South-Western  .            .              ... 

555 

1043 

811 

North-  Western  .            .              ... 

523 

1055 

802 

North-Midland  .            .              ... 

496 

1074 

799 

Wales  

538 

841 

697 

England  and  Wales  (average) 

561 

1444 

867 

It  will  be  seen  that  the  results  brought  out  by  this  table,  are  prac- 
tically identified  with  those  previously  elicited  by  Moore  and  Haviland. 

In  the  supplement  of  the  Fifty-fifth  Annual  Report  of  the  Registrar- 
General,  a  somewhat  similar  table  for  the  counties  is  given  for  the 
decennium  1881-1890  x  ;  but,  in  this  case,  the  mortality  is  for  persons  aged 
thirty-five  years  and  upwards. 

The  counties  with  the  highest  rates  were  : 


Males. 

Females. 

Persons. 

London 

1784 

2667 

2250 

Huntingdonshire 

1916 

2373 

2157 

Cambridgeshire            .            .          . 

1666 

2323 

2012 

Sussex 

1491 

2454 

1999 

Warwickshire               

1533 

2373 

1976 

Those  with  the  lowest  rates  were  : 


Males. 

Females. 

Persons. 

Lancashire 
Durham 
Staffordshire  
Rutlandshire 
Worcestershire 
South  Wales   
Cornwall 
Wilts 

1275 
1227 
1234 
1429 
1213 
1352 
1380 
1122 
1038 
1129 
1143 
1157 

1397 

2092 
2117 
2048 
1874 
2048 
1911 
1855 
2036 
2098 
2095 
1967 
1948 

2261 

1706 
1696 
1663 
1663 
1653 
1647 
1630 
1604 
1597 
1578 
1578 
1574 

1844 

Derbyshire 

Buckinghamshire 
Dorsetshire 
Monmouthshire 

England  and  Wales  (average) 

1  In  the  preceding  decennium  (1871-1880)  the  highest  cancer  rates  for  persons  aged 
twenty-five  years  and  upwards  were  in  London  (1269),  Cambridgeshire  (1193),  Northamp- 
tonshire (1138),  Huntingdonshire  (1138),  Sussex  (1137),  and  Warwickshire  (1095)  5  and 
the  lowest  rates  were  in  Lancashire  (944),  North  Wales  (933),  Dorset  (929),  Monmouth- 
shire (925),  Cornwall  (917),  Durham  (898),  Hertfordshire  (895),  Buckinghamshire  (881), 
South  Wales  (873),  and  Derbyshire  (839). 


82 


THE  NATURAL  HISTORY  OF  CANCER 


The  highest  and  lowest  death-rates  for  all  ages — corrected  for  age  and 
sex  distribution — for  the  same  decennium,  were  met  with  in  the  following 
counties: — the  highest  were  in  Huntingdonshire  (916),  Cambridge- 
shire (789),  Devonshire  (786),  North  Wales  (736),  Sussex  (727),  Nor- 
folk (716),  London  (683)  ;  and  the  lowest  were  South  Wales  (501),  Mon- 
mouthshire (482),  Derbyshire  (482),  Lancashire  (477),  Staffordshire  (475), 
and  Durham  (440). 

In  the  registration  divisions,  the  cancer  death-rates  per  million  living 
of  all  ages  and  both  sexes,  in  1884,  and  in  1900,  were  as  follows  : 


1884. 
.     650     .. 

South-Eastern 
South-Midland    
Eastern    
West-Midland     

.     622     .  . 
.     694     . 
.     763     . 
.     595     . 
.     536     . 

Northern              
South-Western    
North-Western   
North-Midland   
Wales       

.     442     . 
.     642     . 
..     490     . 
.  .     520     . 
.  .     533     . 

1900. 
964 
883 
929 
895 
863 
809 
816 
950 
773 
798 
775 


560 


England  and  Wales  (average)  . . 

In  the  counties,  the  highest  and  lowest  rates  per  million  living  at  all 
js  for  1890,  1900,  and  1901  were  as  follows  : 


1890. 
Both  Sexes. 

1900. 
Both  Sexes. 

1901. 
Males. 

1901. 
Females. 

Huntingdonshire 

1108 

1083 

964 

1300 

Cambridgeshire 

939 

1033 

951 

1330 

North  Wales  

871 

1063 

981 

1200 

Devonshire 

847 

964 

818 

1121 

Norfolk 

781 

991 

879 

1132 

Suffolk 

779 

991 

790 

1031 

Derbyshire 

— 

783 

519 

932 

South  Wales 

563 

658 

577 

798 

Lancashire 

555 

730 

593 

905 

Staffordshire 

538 

685 

482 

802 

Durham 

518 

619 

497 

804 

Monmouthshire 

504 

606 

576 

789 

England  and  Wales  (average) 

676 

828 

691 

985 

The  general  outcome  of  these  data,  which  cover  the  whole  of  the  last 
half  of  the  nineteenth  century,  is  to  show  the  accuracy  of  Moore's  con- 
clusions as  to  the  local  incidence  of  the  disease. 

Another  important  indication  furnished  by  them  is,  that  the  increase 
of  the  disease  has  involved  the  whole  of  the  country,  in  such  a  manner 
that  those  divisions  and  counties,  which  formerly  had  the  highest,  lowest, 
and  medium  cancer  rates,  for  the  most  part,  still  retain  their  peculiarities 
in  these  respects,  although  the  incidence  of  the  disease  has  everywhere 
augmented. 

But,  although  the  local  incidence  of  the  disease  is  thus  shown  to  be 
remarkably  persistent  ;  yet,  in  several  cases,  changes  in  the  comparative 


THE  TOPOGRAPHICAL  DISTRIBUTION  OF  CANCER       83 

proclivity  of  certain  localities  have  occurred  ;  thus,  North  Wales,  where 
the  cancer  mortality  was  formerly  much  below  the  average,  is  now 
subject  to  a  high  rate ;  and  this  change  seems  to  have  coincided  with 
the  invasion  and  settlement  of  the  locality  by  well-to-do  immigrants  from 
the  large  towns  of  Lancashire  and  the  Midlands,  with  their  industrial, 
wealth-producing  innovations  etc. 

The  foregoing  data  refer  exclusively  to  the  death-places  of  cancer 
patients,  which,  of  course,  may  not  correspond  with  their  birth-places. 
By  noting  the  birth-places  of  352  cancer  patients,  I  was  able  to  ascertain 
that  the  localities  where  the  highest  cancer  mortality  obtains,  are  also 
the  localities  where  most  cancer  patients  are  born — thus  confirming 
Nunn's  research  on  the  same  subject.1 

It  is  a  matter  of  importance  to  determine  the  part  played  in  the 
causation  of  these  local  variations  in  the  cancer  mortality,  by  differences 
in  the  age  and  sex  distribution  of  the  population ;  and  the  Registrar- 
General  has  lately  published  data  that  enable  corrections  of  this  kind 
to  be  made.  Although  the  accuracy  of  the  general  results  indicated  by 
the  crude  death-rates  is  not  impugned  by  these  corrections,  yet  the 
comparative  mortality  of  individual  counties  inter  se  is  often  disturbed  ; 
thus,  while  the  crude  cancer  death-rate  of  Huntingdonshire  to  that  of 
Durham  (1881-1890),  was  as  208  to  100,  the  corrected  ratios  are  as  127 
to  100 — yet  the  former  county,  after  correction,  still  retains  its  status  as 
one  of  those  districts  where  cancer  is  most  prevalent,  and  the  latter  as 
one  of  those  where  it  is  least  so. 

Corrected  for  age  and  sex  diversities,  the  counties  with  the  highest 
cancer  rates  are  London,  Huntingdonshire,  Cambridgeshire,  Sussex, 
Warwickshire  etc.  ;  while  those  with  the  lowest  rates  are  Monmouth- 
shire, Derbyshire,  Durham,  Staffordshire,  Lancashire,  South  Wales, 
Dorset,  Bucks,  Wilts,  Cornwall  etc. 

It  is  thus  evident  that  there  are  topographical  variations  in  the 
incidence  of  cancer,  which  are  quite  independent  of  age  and  sex  diver- 
sities ;  and,  it  may  also  be  added,  of  the  disturbing  influence  caused  by 
the  presence  of  large  hospitals. 

Hence,  it  is  exceedingly  improbable  that  the  higher  cancer  mortality 
of  the  agricultural,  as  compared  with  the  industrial  population,  can  be 
explained  as  the  result  of  any  of  the  above-mentioned  disturbing  factors, 
although  such  certainly  exist. 

In  like  manner,  the  average  age  of  the  Irish  population  is  much  higher 
than  that  of  either  England  or  Scotland,  and  the  proportion  of  elderly 
women  it  contains  is  also  greater,  owing  to  the  large  numbers  of  elderly 
people  left  behind  after  the  younger  ones  have  emigrated  ;  yet,  the  cancer 
mortality  of  Ireland  is  much  less  than  that  of  either  England  or  Scotland, 
which  clearly  shows  that  inequalities  in  the  incidence  of  cancer  mortality 
are  determined  by  other  considerations  besides  those  of  age  and  sex 
distribution. 

According  to  Haviland,2  these  variations  are  entirely  due  to  geo- 
logical configuration  and  its  consequences. 

1  For  further  details  vide  my  work  on  "  Diseases  of  the  Breast,"  1894,  p.  256. 

2  Op.  cit. 

6—2 


84  THE  NATURAL  HISTORY  OF  CANCER 

He  maintains  that  the  regions  of  highest  cancer  mortality  are  low- 
lying  districts,  traversed  by,  or  contiguous  to,  rivers  that  seasonally  flood 
the  adjacent  riparial  lands  ;  whereas  the  lowest  cancer  mortality  is  found 
in  high  and  dry  sites,  where  floods  do  not  occur,  and  where  the  subsoil 
consists  of  hard,  non-retentive  rocks — e.g.,  English  lake  district — or  of 
absorbent  substances  like  chalk  and  oolite.  In  support  of  these  views, 
he  instances  the  Thames  and  its  tributaries,  which  run  through  a  vast 
cancer-field ;  and  he  points  to  the  only  localities  in  the  Thames  Valley — 
the  Orsett  and  Dartford  districts — where  there  is  a  low  cancer  mortality, 
as  being  just  those  spots  where  the  chalk  crops  out. 

In  favour  of  the  opinion  that,  in  this  country,  cancer  is  specially  pre- 
valent in  flat,  low-lying,  fenny  districts,  there  is,  I  think,  much  to  be 
said.  The  Forty-seventh  Report  of  the  Registrar-General  shows  that 
Cambridgeshire  and  the  adjacent  counties  of  Northamptonshire,  Hunting- 
donshire, and  Bedfordshire,  all  have  a  very  high  cancer  mortality.  Lin- 
colnshire and  Essex  figure  less  prominently  in  this  Report ;  but  my  analyses 
show  that  the  number  of  cancer  patients  born  in  these  localities  is  exceed- 
ingly high.  This  state  of  things  is  known  to  have  existed  ever  since 
statistical  records  have  been  kept.  In  the  decennial  Report  (1881-1890), 
the  Registrar-General — writing  on  this  subject — says  :  "  Crude  death-rates 
show  that  in  and  around  Huntingdonshire  and  Cambridgeshire,  there  is 
a  well-defined  area  in  which  cancer  is  exceptionally  prevalent.  It  com- 
prises the  districts  of  Stamford,  Bourn,  Spalding,  and  Holbeach  in  Lin- 
colnshire ;  Oundle  and  Peterborough  in  Northamptonshire  ;  and  most  of 
the  counties  of  Huntingdonshire  and  Cambridgeshire.  In  1881-1890  this 
area  had  a  mean  population  of  over  300,000,  its  crude  cancer  rate  being 
857  per  million,  or  46  per  cent,  above  the  average  rate  for  the  country  in 
general ;  in  the  preceding  decennium  the  excess  was  44  per  cent." 

Nevertheless,  I  am  unable  to  accept  Haviland's  views  as  a  sufficient 
explanation  of  the  topographical  variations  in  the  distribution  of  cancer. 
All  low-lying  and  seasonally  flooded  districts  have  not  a  high  cancer 
mortality.  The  very  large  area  drained  by  the  Severn  and  its  tribu- 
taries, for  instance,  is  shown  by  the  Registrar-General's  Forty-seventh 
Report,  to  have  a  low  average  cancer  mortality. 

Moreover,  islands  that  have  no  rivers,  that  are  not  low-lying,  and 
that  are  not  of  alluvial  formation,  nevertheless  have  a  high  cancer  mor- 
tality ;  such  are  the  Scilly  and  Channel  Islands,  and  the  Isle  of  Wight 
may  also  be  mentioned  in  this  connexion. 

The  Scillies  are  small  and  rocky  throughout,  their  total  population 
being  about  2,000  ;  but,  during  the  decennium  1881-1890,  their  cancer 
death-rate  was  considerably  higher  than  that  for  all  England,  and  still 
more  was  it  in  excess  of  that  for  the  adjacent  mainland  (Cornwall). 

The  cancer  death-rate  for  these  islands,  per  10,000  living,  for  the 
decennium  (1881-1890)  was  7-6  (males  2-9,  females  12-2),  the  corre- 
sponding figures  for  aU  England  and  Wales  being  5-8  (males  5-8,  and 
females  7-3). 

For  the  Isle  of  Wight,  the  cancer  death-rate,  in  1900,  was  9-4  per 
10,000  living,  or  1  in  16  of  the  total  mortality. 

A  Jersey  practitioner  having  informed  me  that  cancer  was  very 


THE  TOPOGRAPHICAL  DISTRIBUTION  OF  CANCER       85 

prevalent  there,  as  well  as  in  Guernsey,  I  wrote  to  the  gentleman  who 
furnishes  the  mortality  statistics — such  as  they  are — for  Jersey,  to  the 
Registrar-General ;  but  failed  to  elicit  a  reply. 

Similar  conditions  are  met  with  in  many  inland  districts  ;  thus, 
Dr.  Borrowman,  of  Elie,  in  Fifeshire,  N.B.,  writes  to  me  :  "  It  will  interest 
you  to  know  that  cancer  is  very  common  here.  Between  11  and  12  per 
cent,  of  my  patients  have  died  from  malignant  disease.  This  is  a  par- 
ticularly dry  part  of  the  country.  There  are  no  rivers  at  all  in  the 
district ;  and  the  few  streams  that  do  exist  have  a  good  fall.  Flooded 
land  is  quite  unknown  here." 

In  other  countries  this  peculiarity  has  also  been  noted ;  thus,  cancer 
is  very  prevalent  in  the  Ballarat  gold-field  region  of  Victoria,  where  no 
rivers,  no  alluvial  valleys,  and  no  malaria  occur,  the  whole  country  being 
a  volcanic  plateau,  from  which  the  rain  drains  away  as  soon  as  it  has. 
f  alien,  i 

Recently  attempts  have  been  made  by  the  microbists,  to  explain  these 
topographical  variations  as  the  outcome  of  contagion ;  but,  the  peculiar 
manner  in  which  this  malady  is  distributed  throughout  the  whole  country, 
and  the  constancy  with  which  the  various  local  incidence  ratios  have  been 
maintained  from  decennium  to  decennium,  notwithstanding  the  universal 
increase,  tells  against  this  theory,  the  general  inadequacy  of  which  I  shall 
subsequently  have  occasion  to  point  out . 

It  appears  to  me  that  the  explanation  of  these  variations  must  be 
sought,  in  the  conditions  of  life  peculiar  to  the  respective  populations. 

Let  us  now  carefully  examine  the  vital  statistics  of  our  country  for 
the  last  half-century,  in  order  to  determine  the  particular  conditions 
which  have  tended  to  this  end.  Such  an  examination  shows — as  I  have 
previously  indicated — that  the  cancer  mortality  is  lowest  where  the 
struggle  for  existence  is  hardest,  the  density  of  population  greatest,  the 
tubercle  mortality  highest,  the  birth-rate  highest,  the  average  duration 
of  life  shortest,  the  infantile  and  general  mortality  highest,  and  where 
sanitation  is  least  perfect — in  short,  among  the  poor  of  the  industrial 
classes  in  our  large  towns  ;  whereas,  among  the  wealthy  and  well-to-do — 
where  the  standard  of  health  is  at  its  best,  and  life  is  easiest,  and  all  the 
conditions  of  existence  are  just  the  converse  of  the  foregoing — and  among 
the  agricultural  community,  there  the  cancer  mortality  is  highest. 
Other  things  being  equal,  there  are,  in  my  opinion,  no  more  potent 
factors  in  the  causation  of  cancer  than  high  feeding  and  easy  living. 
Hence  it  is  that  the  cancer  mortality  of  mining  and  industrial  centres, 
like  South  Wales,  Monmouthshire,  Lancashire,  Durham,  Derbyshire, 
Staffordshire,  Cornwall,  West  Riding,  etc.,  is  so  low  ;  and  that  it  contrasts 
so  favourably  with  the  cancer  mortality  of  the  generality  of  agricultural 
districts.  Although  the  ratio  of  pauperism  in  the  rural  districts  is  quite 
double  that  of  the  industrial  ones,  I  have  no  hesitation  in  saying,  as  the 
result  of  my  own  observation  of  life  under  both  conditions,  that  so  far 
as  food  and  comfort  are  concerned,  the  average  agricultural  labourer  is 
much  better  off  during  his  working  years  than  his  confrere  of  the  industrial 
army.  As  a  proof  of  this,  it  may  be  mentioned  that  the  average  duration 
1  J.  H.  Well,  Lancet,  vol.  ii.,  1901,  p.  976. 


86  THE  NATURAL  HISTORY  OF  CANCER 

of  the  agricultural  labourer's  life,  is  more  than  double  that  of  his  mate 
in  the  large  towns  ;  and  his  wages  and  general  conditions  of  existence 
have  greatly  improved  during  the  last  half-century.  On  this  subject  a 
leading  London  newspaper  remarked  :l  "  The  material  prosperity  of  the 
agricultural  labourer  is,  and  has  been,  during  recent  years,  higher 
than  at  any  period  during  the  last  century.  The  slight  falling-off  in  the 
amount  of  his  wages  is  more  than  compensated  for  by  their  increased 
purchasing  power.  All  the  necessaries  of  life,  during  the  last  thirty  years, 
have  become  much  cheaper — meat,  bacon,  cheese,  tea,  sugar,  butter, 
and  coal — the  difference  being  something  like  25  per  cent,  in  favour  of 
the  buyer." 

Provincial  towns  with  the  highest  cancer  death-rates  per  100,000 
living,  during  the  decennium  1881-1890  are  : — Chichester  (118),  Canter- 
bury (113),  Bala  (107),  Huntingdon  (106),  Exeter  (101),  Saffron-Walden 
(99),  Cirencester  (97),  Cambridge  (95),  St.  Asaph  (94),  Dolgelly  (94), 
Buckingham  (94),  Bath  (93),  Scarborough  (93),  Holbeach  (92),  Devizes 
<91),  Bury  St.  Edmunds  (90)  etc. 

It  is -noteworthy  that  this  list  does  not  include  a  single  great  industrial 
-centre,  the  places  named  being  well-to-do,  easy-going,  residential  country 
towns. 

For  the  great  industrial  centres  the  rates  are  much  less,  viz.,  Bristol 
(83),  Birmingham  (72),  Liverpool  (69),  Manchester  (67),  Leeds  (62),  New- 
castle (55),  Derby  (52),  Sheffield  (50),  Salford  (48),  Wolverhampton  (47), 
Cardiff  (45),  West  Ham  (40),  Bolton  (40),  Blackburn  (38),  Durham  (32) 
etc. 

In  London  and  its  vicinity,  where  the  wealth  of  the  nation  is  clotted, 
there  the  cancer  mortality  is  highest ;  and  it  is  significant  that  this 
mortality  is  highest  of  all  in  those  parts  of  the  metropolis  and  its  suburbs, 
where  the  well-to-do  most  abound.  Thus,  for  1903,  the  highest  cancer 
rates  were  in  wealthy  Hampstead,  Marylebone,  Chelsea,  and  Westminster  ; 
while  the  lowest  were  in  the  poor  industrial  districts  of  Bermondsey, 
Stepney,  Bethnal  Green,  Poplar,  and  in  the  poverty-stricken  extra-metro- 
politan district  of  West  Ham.  Crude  rates  show,  that  the  disease  is 
very  much  more  prevalent  in  the  former  than  in  the  latter  group  of  com- 
munities. Corrections  for  age  and  sex  diversities,  for  hospitals  and  other 
public  institutions,  although  they  somewhat  mitigate  these  extremes,  still 
show  that  the  cancer  mortality  is  much  less  in  the  poor  industrial  districts, 
than  it  is  in  those  inhabited  by  the  wealthy  and  well-to-do.  Moreover, 
a  similar  state  of  things  is  noticeable  in  all  our  large  towns  (as  I  have 
previously  indicated  in  the  case  of  Bristol),  and  throughout  the  country 
in  general. 

In  other  European  countries,  where  sufficiently  detailed  statistics 
have  been  kept,  similar  topographical  variations  in  the  incidence  of  the 
disease  are  everywhere  noticeable. 

1  Standard,  August  12,  1897. 


CHAPTER  V 
CANCER   AND   OTHER   TUMOURS   IN   ANIMALS 

Some  General  Remarks  on  Tumours  in  Animals. 

CONSIDERING  the  great  advances  lately  made  in  most  branches  of  biology, 
the  stagnation  of  comparative  pathology  is  a  surprising  and  regrettable  *  " 
anomaly ;  for,  many  of  the  most  important  pathological  problems  now  <**/'< 
pending,  might  be  more  profitably  investigated  by  this  method,  than  by  \\ 
the  experimental  or  other  dispersive  analytical  procedures,  now  so  much  •,»>. 
in  vogue.  ft* 

Although  progress  has  lately  been  made,  the  comparative  pathology 
of  tumours  is  still  in  a  rudimentary  and  backward  condition. 

Some  important  conclusions  have,  however,  already  been  estab- 
lished. 

Morphological  and  physiological  processes  being  similar  in  the  animal 
world  and  in  mankind,  it  is  only  reasonable  to  suppose  that  pathological 
processes  will  also  manifest  a  certain  similarity  ;  and,  from  what  is 
known  of  the  diseases  of  animals,  this  supposition  appears  to  be  fully 
justified,  at  any  rate,  so  far  as  tumours  are  concerned,  it  has  been 
ascertained  that  the  analogy  holds  good. 

In  vegetable  organisms,  physiological  and  pathological  processes  are 
certainly  much  less  complex  than  in  animals,  if  only  in  that  the  former       > 
are  destitute  of  nerve  and  lymph- vascular  systems,  which  add  so  much 
to  the  difficulty  of  disentangling  the  genesis  of  vital  processes  in  the 
latter. 

As  I  have  shown  in  my  book  on  the  "  Principles  of  Cancer  and  Tumour 
Formation,"  which  was  published  in  1888,  the  really  fundamental  physio- 
logical and  pathological  processes  are  the  same  in  plants  as  in  animals  ; 
and  it  accords  with  this,  as  I  have  indicated  in  the  above-mentioned 
work,  that  malignant  and  other  tumours  also  originate  in  vegetable 
organisms. 

We  thus  arrive  at  the  important  conclusion,  that  tumours  may  arise, 
under  certain  circumstances,  in  any  multicellular  animal  or  vegetable 
being.  ; 

Another  consideration  to  which  I  have  previously  called  attention  is,  J-H?" 
that  these  abnormalities  very  rarely  affect  organisms  living  in  a  state  of  ^/ 
nature.     It  is  almost  exclusively  among  domesticated  varieties,  among 
those  that  have  been  kept  long  in  confinement,  or  that  have  been  other- 
wise abnormally  circumstanced,  that  tumours   are   met  with  ;  thus,  in 
savages  and  wild  animals,  tumours  very  rarely  occur. 

87 


88  THE  NATURAL  HISTORY  OF  CANCER 

Nearly  all  of  those  who  have  specially  studied  the  comparative  inci- 
dence of  tumours  in  animals  and  mankind,  are  agreed  that  these  maladies 
are  relatively  infrequent  in  the  former ;  and  this  appears  to  me  to  be  due 
to  the  fact,  that  animals  have  been  much  less  extensively  subjected  to 
the  influence  of  domestication,  and  to  such  other  abnormal  conditions  of 
existence  as  I  have  above  referred  to,  than  mankind.  At  any  rate,  it  is 
remarkable  that  nearly  all  the  examples  of  animal  tumours  hitherto 
reported,  have  been  met  with  in  our  common  domesticated  species. 

Recent  observations  as  to  the  relative  frequency  of  malignant  tumours 
in  the  latter,  show  that  these  maladies  are  not  so  rare  as  was  formerly 
believed  :  thus,  Veterinary-Inspector  Trotter  found  that  of  47,362  cattle, 
slaughtered  at  Glasgow  in  1903,  131  had  some  form  of  malignant  tumour, 
or  2-8  per  1,000,  the  corresponding  ratio  for  English  humanity  being 
about  60  per  1,000. 

All  the  indications  at  present  available  point  to  the  great  rarity  of 
cancer  in  wild  animals,  whether  living  in  confinement  or  under  natural 
conditions  ;  indeed,  but  very  few  instances  of  this  kind  have  so  far  been 
reported. 

Of  2,647  wild  mammals  comprised  in  the  New  York  Zoo,  during  a 
period  of  five  years,  H.  Brooks  *  reports  that  not  a  single  specimen  of 
tumour  was  met  with,  although  they  were  specially  examined  ad  hoc. 
A  large  proportion  of  these  animals  had  only  recently  been  reduced  to 
captivity.  Of  those  which  died,  744  were  submitted  to  thorough  post- 
mortem examination ;  yet,  only  a  single  case  of  malignant  tumour  was 
found,  viz.,  sarcoma  of  the  ovary  of  a  wild,  white,  racoon-dog  (Nyctereutes 
albus),  from  the  north  of  Japan,  which  sickened  and  died  emaciated  after 
a  sojourn  of  two  years  in  the  Zoo. 

Under  these  circumstances,  it  seems  to  me  that  the  dictum  of  the 
Cancer  Research  Fund  2  as  to  the  incidence  of  cancer  in  animals  approxi- 
mating in  frequency  to  that  in  mankind  must  be  rejected,  as  being  with- 
out scientific  warrant. 

In  respect  to  such  conditions  as  the  foregoing,  there  is  some  analogy 
between  the  incidence  of  tumours  and  developmental  anomalies ;  for  the 
latter,  like  tumours,  are  relatively  rare  in  savages  and  wild  organisms  ; 
whereas,  they  are  common  in  mankind,  in  domesticated  organisms,  and 
in  those  that  have  been  kept  long  in  confinement,  or  that  have  been 
otherwise  abnormally  circumstanced. 

In  this  connexion,  I  must  call  attention  to  another  noteworthy  con- 
comitant of  the  augmented  British  cancer  mortality,  viz.,  the  great 
increase  in  the  incidence  of  congenital  defects  and  premature  births,  as 
to  which  I  shall  subsequently  have  to  refer  more  in  detail. 

Thus,  whatever  the  causes  of  malignant  tumours  may  be,  they  are 
not  limited  to  mankind — as  John  Hunter,  Camper,  Otto,  and  some  other 
pathologists  believed — nor  even  to  the  animal  world,  as  most  modern 
pathologists  even  now  suppose. 

From  such  facts  as  have  already  been  ascertained  with  regard  to 
tumours  in  animals,  it  may  be  confidently  predicted,  that  all  the  varieties 

1  American  Journal  of  Medical  Science,  May,  1907,  p.  769. 

2  Scientific  Reports  of  the  Imperial  Cancer  Research  Fund,  No.  2,  part  i.,  1905. 


CANCER  AND  OTHER  TUMOURS  IN  ANIMALS  89 

of  the  neoplastic  process  recognized  in  mankind  have  their  counterparts 
in  the  animal  world. 

It  appears  to  me  that  the  chief  feature  in  which  animal  tumours 
differ  from  their  human  congeners,  is  in  respect  to  the  relative  frequency 
of  site  incidence  ;  and  this  I  suspect  is  mainly  the  outcome  of  diversity 
of  function  and  structure  in  certain  organs,  which,  in  their  turn,  ulti- 
mately depend  upon  differences  in  habit  and  mode  of  life — for  such  influ- 
ences are  as  potent  in  pathology,  as  in  physiology. 

In  the  first  place,  it  is  noticeable  that  the  connective-tissue  type  of 
malignant  tumour,  which  in  mankind  comprises  only  from  6  to  15  per 
cent,  of  all  malignant  growths,  in  animals  is  at  least  as  frequent  as  the 
epithelial  form,  and  some  pathologists  consider  that  it  is  more  frequent. 

Johne  found,  as  the  result  of  post-mortem  examination,  that  sarco- 
mata comprised  47  per  cent,  of  the  total  tumours  met  with  in  horses, 
37  per  cent,  in  cattle,  and  28  per  cent,  in  dogs  ;  while  the  corresponding 
figures  for  malignant  epithelial  tumours  were,  22  per  cent,  for  horses, 
8  per  cent,  for  cattle,  and  52  per  cent,  for  dogs. 

With  regard  to  the  site  incidence  of  malignant  tumours  in  animals,  as 
compared  with  human  beings,  the  most  striking  fact  is  the  comparative 
rarity  of  these  tumours  in  many  localities,  where  they  are  of  very  frequent 
occurrence  inhumanity — e.g.,  the  stomach,  liver,  uterus,  intestine,  tongue, 
and  mouth. 

The  comparative  rarity  of  gastro-intestinal  types  of  cancer  in  animals 
is  very  marked ;  thus,  1,312  cases  of  cancer  in  common  domestic  animals 
(horse,  ox,  dog,  sheep,  cat,  and  pig),  as  tabulated  by  Sticker  *•  (1,170  cases), 
Bashford,  McFadyean,  Cadiot  and  Roger,  comprise  only  twenty  instances 
of  malignant  disease  of  the  stomach,  or  about  1-5  per  cent.  ;  whereas,  for 
human  beings,  the  corresponding  figure  is  about  17  per  cent.  :  in  like 
manner,  the  same  series  comprises  only  42  cases  of  malignant  disease  of 
the  liver,  or  3-2  per  cent.  ;  whereas,  in  mankind,  the  corresponding  per- 
centage is  about  13-5.  The  only  form  of  gastro-intestinal  malignant 
disease  at  all  common  in  these  animals,  is  that  which  affects  the  anus,  of 
which  there  were  97  examples,  or  7-4  per  cent.,  a  figure  greatly  in  excess 
of  the  corresponding  human  ratio,  for  I  have  found  that  only  0-37  per 
cent,  of  human  cancers  are  thus  situated.  This  anal  form  of  malignant 
disease  is  of  more  frequent  occurrence  in  the  dog,  than  in  any  other  of 
the  animals  mentioned  ;  for,  of  738  canine  cancers,  Sticker  found  that  89, 
or  12  per  cent.,  were  thus  located. 

The  rarity  of  lingual  cancer  in  these  animals  may  be  judged  from  the 
fact,  that  only  four  examples  are  comprised  in  the  1,312  cases,  or  0-3  per 
cent.  ;  to  these  may  be  added  16  cases  of  cancer  in  the  mouth  (chiefly 
of  the  gums).  Thus,  we  get  20  cases  of  cancer  of  the  tongue  and  mouth, 
or  1-5  per  cent.,  the  corresponding  figure  for  humanity  being  3-5  per 
cent. 

Only  26  cases  of  uterine  malignant  disease — all  from  Sticker's  list — 
are  comprised  in  these  1,312  cases,  or  about  2  per  cent,  of  the  total,  the 
corresponding  figure  for  humanity  being  about  12  per  cent. 

By  way  of  contrast  with  the  foregoing,  mammary  cancers  are  of 

1  Arch.  f.  klin.  Chir.,  1902,  Bd.  Ixv.,  pp.  616,  1023. 


90  THE  NATURAL  HISTORY  OF  CANCER 

'  commoner  occurrence  in  these  animals  than  in  mankind  ;  for,  of  the  1,312 
animal  tumours,  no  less  than  360  were  thus  located,  or  27-4  per  cent., 
the  corresponding  figure  for  humanity  being  only  8  per  cent.  This 
frequency  of  mammary  cancer  in  these  animals,  is  due  to  the  great  pre- 
ponderance of  this  form  in  dogs,  as  shown  by  Sticker's  list,  which  com- 
prises 341  cases  of  canine  mammary  cancer  in  a  total  of  738  malignant 
tumours  in  dogs,  or  46  per  cent. 

Cutaneous  manifestations  of  the  disease  comprise  16  per  cent,  of  the 
animal  series,  this  localization  being  of  very  frequent  occurrence  in  dogs  ; 
whereas,  in  humanity,  skin  cancers  comprise  only  about  2-5  per  cent,  of 
the  total  cases. 

According  to  Johne,  most  sarcomata  in  animals  originate  from  the 
bones. 

It  will  be  gathered  from  the  foregoing,  that  the  usual  seats  of  traumata 
and  mechanical  injuries,  rarely  coincide  with  the  site  incidence  of  malignant 
tumours  in  animals. 

With  regard  to  the  sex  incidence  of  the  disease  in  animals,  there  is  a 
dearth  of  really  satisfactory  data ;  but,  available  indications  point  to  the 
conclusion  that  there  is  no  such  great  diversity  between  the  sexes  in  this 
respect,  as  is  the  case  with  humanity ;  and  from  this  it  may  be  inferred, 
that  the  greater  proclivity  of  the  human  female  is  due  rather  to  circum- 
stances connected  with  her  special  sheltered  environment,  than  to  any 
peculiarity  directly  connected  with  sex.  It  accords  with  this,  that 
malignant  tumours  are  of  common  occurrence  in  castrated  domestic 
animals  of  both  sexes. 

It  has  been  suggested  that  the  immunity  of  animals  from  uterine 
tumours — malignant  or  otherwise — as  compared  with  humanity,  may  in 
some  way  be  due  to  the  absence  of  menopause,  in  which  they  differ  from 
human  females. 

In  humanity,  as  I  shall  subsequently  have  occasion  to  show,  the 
characteristic  feature  of  the  age  incidence  of  cancer,  is  not — as  is  generally 
believed — its  increase  with  advance  of  years ;  but,  rather,  its  dispropor- 
tionate augmentation  in  the  post-meridian  periods  of  life — the  liability  to 
the  malady  waxing  as  the  developmental  and  reproductive  activities  wane. 

In  the  animal  world,  the  age  incidence  of  cancer  is  governed  by  a 
similar  law,  tumours  of  this  kind  being  very  rare  in  early  life,  commonest 
in  post-meridian  ages,  and  less  frequent  in  advanced  age,  as  Sticker's 
data  show  ;  thus,  of  134  dogs  affected  with  malignant  tumours,  he 
found  that  only  one  was  young,  107  were  middle-aged,  and  26  were 
extremely  old  etc.1 

Very  few  instances  of  congenital  malignant  tumours  in  animals  are 
known  to  me,  but  Penberthy 2  has  met  with  sarcoma  of  the  chest  wall 
in  a  newly  born  foal ;  and  Crisp  has  seen  a  large  encephaloid  tumour  on 
the  chest  of  a  lamb. 

1  Of  70  dogs  with  malignant  epithelial  tumours,  the  ages  were  as  follows  :— 2  to  3  years 
in  14'3  per  cent.  ;  5  to  6  years  in  25  per  cent.  ;  7  to  8  years  in  28  per  cent. ;  9  to  10  years 
in  20  per  cent.  ;  11  to  15  years  in  1T4  per  cent.    Of  90  horses  similarly  affected,  the  age 
percentages  were  as  follows  : — under  4  years  old  2'2  ;  5  to  6  years  4'2  ;  7  to  8  years  10  ; 
9  to  10  years  15'5  ;  11  to  12  years  9  ;  13  to  14  years  11  ;  15  to  16  years  17'7  ;  17  to  18 
years  12'2  ;  19  to  20  years  14  4  ;  23  to  25  years  5'3. 

2  Journ.  Comp.  Path.,  etc.,  1902,  vol.  xv.,  p.  271. 


CANCER  AND  OTHER  TUMOURS  IN  ANIMALS  91 

Examples  of  tumours,  malignant  and  otherwise,  have  now  been 
demonstrated  in  all  classes  of  vertebrata  ;  and — although  at  the  present 
time  the  pathology  of  the  invertebrata  is  practically  terra  incognita — it 
seems  probable  that  in  the  future  similar  tumours  will  be  shown  to  occur 
in  this  division  also  ;  indeed,  a  beginning  has  already  been  made,  for 
J.  W.  Williams  *•  has  described  an  instance  of  a  pediculated  tumour,  com- 
prising muscular  and  glandular  elements,  in  a  fresh- water  mussel  (Ano- 
donta  cygnea),  and  similar  tumours  have  been  noted  by  Collinge.2  Ryder,3 
in  an  oyster,  has  also  met  with  a  large  tumour  ;  and,  as  is  now  generally 
recognized,  the  formation  of  pearls  is  due  to  a  formative  process  excited 
by  the  presence  of  some  foreign  body,  often  a  parasite.  Invertebrate 
animals  are  also  very  prone  to  pseudo-plasms,  caused  by  parasitic 
sporozoa  etc. 

The  very  frequent  occurrence  of  malignant  tumours  in  castrated 
animals  of  both  sexes  shows,  that  ablation  of  the  essential  sex  glands 
has  no  deterrent  power  whatever  on  the  onset  of  this  malady,  but  there 
are  rather  indications  that  these  mutilations  favour  its  development ; 
thus,  nearly  50  per  cent,  of  the  horses  affected  with  cancer  in  Sticker's 
list,  had  been  castrated. 

In  the  animal  world,  even  more  than  in  mankind,  malignant  tumours 
are  apt  to  be  confounded  with  various  pseudo-plasms  of  "chronic  in- 
flammatory," tuberculous,  microbic,  aspergillary,  or  of  unknown  infec- 
tive origin ;  and,  mistakes  of  this  kind  are  all  the  more  prevalent,  because 
the  comparative  pathology  of  animals  has  hitherto  been  but  little  studied. 
As  an  example  of  this,  reference  may  be  made  to  Wehr's  4  experiments 
as  to  the  transmissibility  of  "  cancer  "  from  dog  to  dog,  which  attracted 
so  much  attention  a  few  years  ago ;  the  so-called  "  cancer  "  in  this  case 
being  nothing  but  a  previously  unrecognized  kind  of  venereal  pseudo- 
plasm  of  unknown  aetiology,  but  certainly  not  cancerous. 

In  all  probability  the  present  hasty  identification  of  "  Jensen's 
tumour" — which  is  transmissible  from  mouse  to  mouse — with  cancer,  is 
destined  to  furnish  another  memorable  example  of  the  saine  kind  of 
mistake. 

According  to  Rayer5  and  Leblanc,  among  the  older  comparative 
pathologists,  carnivorous  animals  are  more  prone  to  malignant  tumours 
than  herbivorous  ones  ;  whereas,  with  regard  to  tubercle,  the  relative 
liability  is  just  the  converse.  In  support  of  this  contention  Raye^r  found 
that  cancer  was  common,  and  tubercle  rare,  among  birds  of  prey  ;  while, 
among  non-carnivorous  birds,  tubercle  was  the  prevalent  malady,  and 
cancer  was  unusual.  In  support  of  this  observation,  it  may  be  men- 
tioned that  Rayer's  contemporary,  E.  Rousseau,  found  that  eagles  and 
vultures,  confined  in  the  Jardin  des  Plantes  at  Paris,  not  infrequently 
succumbed  with  cancer. 

Among  those  who  have  lately  investigated  this  subject,  Johne,  Woods 
Hutchinson,  Schutz,  Pick  and  Poll,  support  Rayer's  view. 

1  Journ.  of  Anat.,  1890,  vol.  xxiv.,  p.  307. 

2  Ibid.,  1891,  vol.  xxv.,  p.  154. 

3  Proc.  Acad.  Nat.  Sci.,  Philadelphia,  U.S.,  1887. 

4  Arch.  f.  klin.  Chir.,  1889,  Bd.  xxxix.,  S.  226. 
6  Arch,  de  med.  comparee,  1843. 


92  THE  NATURAL  HISTORY  OF  CANCER 

In  this  connexion,  it  is  significant  that  among  our  common  domestic 
animals,  malignant  tumours  are  of  much  more  frequent  occurrence  in 
dogs,  than  in  any  others  ;  thus,  of  1,312  cases  of  malignant  tumours  in 
domestic  animals  tabulated  by  Sticker  etc.,  no  less  than  810  were  in 
dogs.  Cats  are  also  very  liable  to  cancerous  tumours. 

In  the  animal  world  tubercle  is  a  common  disease,  especially  with 
our  domesticated  bovines  and  birds. 

All  of  these  facts,  as  well  as  others  to  which  I  have  already  referred, 
indicate  the  important  part  played  by  the  conditions  of  existence  in 
determining  the  incidence  of  cancer  ;  and,  among  these  conditions,  nutri- 
tion is  one  of  the  most  important.  In  my  opinion,  Dr.  Bashford  showed 
extraordinary  lack  of  understanding  of  biological  principles  and  scientific 
insight,  when  he  wrote  i1  "  The  great  diversity  of  food,  habit,  and  condi- 
tions of  life  generally  in  animals  in  which  cancer  occurs,  shows  that  such 
external  agencies  have  no  causative  influence." 

With  regard  to  non-malignant  tumours,  it  is  noticeable  that  exostoses 
and  osteomata  are  very  common  in  all  classes  of  vertebrata,  even  in 
reptiles  and  fishes.  Papillomata  are  also  of  frequent  occurrence  in 
animals.  Adenomata  are  comparatively  rare,  except  in  the  mamma  of 
dogs.  Fibrous  and  fatty  tumours  are  also  extremely  rare  in  animals, 
wild  or  domesticated.  When  we  recollect  that  most  of  our  domestic 
animals  have  been  bred  for  thousands  of  years,  with  special  reference  to 
fattening,  this  rarity  of  fatty  tumours  is  all  the  more  remarkable. 


Monkey. 

X  Great  interest  attaches  to  the  maladies  of  monkeys,  because  it  is 
among  the  highest  members  of  this  order  that  we  find  the  nearest  approach 
in  organization  to  mankind. 

Notwithstanding  the  immense  number  of  these  creatures  constantly 
under  observation  in  the  zoological  collections  of  Europe,  it  is  a  curious 
fact  that  only  about  half  a  dozen  examples  of  tumours  have  hitherto 
been  reported,  and  their  comparative  immunity  from  this  kind  of  malady 
seems  to  be  a  reality. 

Thus,  some  time  ago,  Bland-Sutton2  examined  the  bodies  of  110  of 
these  animals  which  had  died  in  the  London  Zoo,  but  not  a  single  example 
of  any  tumour  did  he  find.  Subsequently,  H.  J.  Campbell3  made  thirty- 
eight  similar  post-mortem  inspections,  with  the  like  negative  result. 

Leblanc,4  however,  long  ago  reported  that  he  had  met  with  instances 
of  malignant  tumours  in  monkeys,  and  I  expect  that  they  do  occasionally 
occur ;  but  I  can  cite  only  two  modern  instances. 

The  first  of  these  is  due  to  Goodhart,5  who  found  "  cancer  "  of  the 
pituitary  body  in  an  Anubis  baboon,  from  the  London  Zoo,  where  the 
animal  had  long  been  a  familiar  denizen.  The  tumour — a  large,  ragged- 

1  Second  Annual  Report  Imperial  Cancer  Research  Fund,  1904. 

2  Lancet,  1883,  vol.  ii.,  p.  276. 

3  Guy's  Hospital  Reports,  1891,  vol.  xlviii.,  p.  19. 
*  Clin.  Vet.,  August,  1843,  p.  343. 

6  Transactions  of  the  Pathological  Society,  London,  1883,  vol.  xxxvi.,  p.  36. 


CANCER  AND  OTHER  TUMOURS  IN  ANIMALS  93 

looking  object — occupied  the  pituitary  fossa,  which  it  had  eroded,  and 
some  of  the  adjacent  structures  were  infiltrated.  Histologically  it  com- 
prised "  large  epithelial- like  cells  arranged  in  some  sort  of  an  alveolar 
manner."  There  were  no  secondary  deposits.  This  tumour,  together 
with  the  brain  and  skull,  are  preserved  in  the  museum  of  the  Royal 
College  of  Surgeons. 

The  second  instance  was  met  with  in  a  bonnet  monkey,  only  eight 
months  old,  by  Bland-Sutton,1  the  tumour  being  an  intra-ocular  glioma, 
consisting  chiefly  of  small  round  cells. 

Here  also  mention  may  be  made  of  a  curious  atypical  epithelial 
growth  of  the  cervix  uteri  of  a  monkey  by  Woods  Hutchinson,2  who  was 
in  doubt  whether  it  was  an  adenoma  or  a  carcinoma. 

In  this  connexion  reference  may  be  made  to  the  attempts  of  Shattock 
and  Ballance,  Metchnikoff,  and  others,  to  transmit  human  cancer  experi- 
mentally  to  monkeys,  all  of  which  experiments  failed. 

Thus,  monkeys,  like  human  savages,  seem  to  have  very  little  pro- 
clivity to  cancer. 

Here  it  may  be  remarked  that  the  alimentary  propensities  of  these 
animals  are  predominantly  frugivorous,  but  a  good  many  of  them  are 
not  averse  to  animal  food  when  they  can  get  it.  Some  kinds  are  insecti- 
vorous, and  others  feed  upon  almost  anything  they  can  get.  As  with 
mankind,  many  species  have  a  singular  liking  for  birds  and  their  eggs, 
as  alimentary  dainties. 

With  regard  to  non-malignant  tumours,  the  available  data  are 
exceptionally  meagre. 

Bland-Sutton  has  met  with  an  instance  of  leio-myomatous  thickening 
in  the  uterus  of  a  baboon,  which  had  some  resemblance  to  myoma ;  and 
the  same  observer  has  also  seen  a  fatty  tumour-like  mass  in  the  vicinity 
of  each  testis  of  a  monkey  with  hermaphroditic  malformation. 

According  to  Otto,  exostosis  is  not  uncommon  at  the  tip  of  the  tail 
of  long-tailed  monkeys  ;  and,  in  the  museum  of  the  Royal  College  of 
Surgeons  of  Ireland  the  hand  of  a  monkey  is  preserved,  showing  a  spongy 
exostosis  of  the  first  phalanx  of  the  little  finger. 

Monkeys  are  also  subject  to  hydatid  cysts.    M 

These  few  examples  practically  exhaust  our  present  knowledge  of 
non-malignant  tumours  in  monkeys. 

It  is  an  ancient  belief  that  monkeys  in  captivity  are  very  prone  to 
tubercle ;  and,  some  years  ago,  a  mild  sensation  was  experienced  when 
Bland-Sutton  3  flatly  contradicted  this  cherished  conception.  In  justifica- 
tion of  his  contention,  he  appealed  to  the  record  of  110  post-mortem 
inspections  of  monkeys,  which  had  died  in  the  London  Zoo,  and  comprised 
only  three  instances  of  tubercle.  He  found,  however,  that  these  animals 
had  experienced  very  heavy  mortality  from  diseases  of  the  lungs — the  list 
comprising  22  examples  of  bronchitis,  11  of  pneumonia,  etc. 

Some  years  later  H.  J.  Campbell,4  as  the  result  of  similar  work  in  the 
same  field,  arrived  at  exactly  the  opposite  conclusion,  having  found  that 

1  Journ.  of  Anal,  and  Physiol.,  1885,  vol.  xix.,  p.  449. 

2  "  Human  and  Comparative  Pathology,"  1901,  p.  258. 

3  Lancet,  1883,  vol.  ii.,  p.  276.  *  Op.  cit. 


94  THE  NATURAL  HISTORY  OF  CANCER 

tuberculous  disease  was  very  frequent  in  these  monkeys.  Thus,  no  less 
than  20  of  the  38  bodies  he  examined,  presented  well-marked  tuberculous 
lesions.  In  addition  to  these,  there  were  also  many  cases  of  broncho- 
pneumonia. 

It  is  evident  that  these  discrepancies  depend  mainly  upon  diversity 
as  to  the  criterion  of  tubercle.  Viewing  the  matter  in  this  light,  we  shall 
probably  be  right  in  maintaining  the  validity  of  the  old  belief. 

In  support  of  this,  reference  may  be  made  to  the  observations  of 
Dr.  A.  J.  Harrison,1  who  has  long  been  connected  with  the  management 
of  the  fine  collection  of  animals  at  the  Clifton  Zoo.  He  says  :  "  Monkeys 
are  very  liable  to  chest  affections,  and  there  can  be  no  question  that 
we  have  lost  a  great  many  from  tuberculous  disease  of  the  lungs.  They 
seem  very  prone  to  pleurisy,  and  adhesions  are  frequently  found  with 
and  without  tuberculous  masses  in  the  lungs  ;  but  actual  cavities  do  not 
seem  to  be  frequent.  Monkeys  seem  to  be  particularly  prone  to  tubercle." 

It  accords  with  the  foregoing,  that  Lydia  Rabinowitsch  2  has  lately 
found  many  examples  of  tubercle  among  the  monkeys  that  died  in  the 
Berlin  Zoo  ;  and,  of  36  cases  in  which  these  lesions  were  specially  examined 
ad  hoc,  in  nearly  three-fourths  the  type  of  tubercle  was  human,  examples 
of  bovine,  avian,  and  mixed  types  being  only  occasionally  met  with. 

It  has  likewise  been  proved  that  monkeys  are  very  susceptible  to  the 
experimental  inoculation  of  both  the  human  and  bovine  forms  of  tubercle, 
as  the  experiences  of  Dieulafoy,  Krishaber,  Dungern,  and  others  testify. 

Of  like  import  is  the  common  occurrence  of  specimens  of  simian 
tuberculous  disease  in  museums,  such  as  that  of  the  Royal  College  of 
Surgeons  of  Ireland,  which  have  good  collections  illustrative  of  the 
pathology  of  these  animals. 

According  to  Woods  Hutchinson,3  monkeys  in  their  native  forests 
are  but  little  prone  to  tubercle  ;  but,  in  captivity,  it  is  difficult  to  procure 
specimens  free  from  the  disease.  Thus,  of  45  monkeys  that  died  in 
captivity  at  the  London  Zoo  (1898-1899),  17  died  of  tubercle,  or  38  per 
cent.  Food  habits  have  much  to  do  with  tubercle  mortality ;  for,  of 
Hutchinson's  animals,  35  were  vegetarian  Catarrhines,  and  it  was  among 
these  that  all  the  17  deaths  occurred ;  whereas,  not  one  of  the  ten  deaths 
among  the  Platyrrhine  monkeys,  who  had  taken  a  fair  amount  of  animal 
food,  was  due  to  tubercle. 

Dog. 

Of  all  domesticated  animals,  dogs  are  by  far  the  most  prone  to  malig- 
nant tumours  ;  thus,  of  60,471  canine  patients  at  the  Berlin  thierartz- 
lichen  Hochschiile  (1886-1894),  Frohner*  found  that  2,871  had  some 
form  of  tumour,  of  which  1,154  were  cancerous,  or  1-9  per  cent,  of  the 
total ;  of  1,306  dogs  examined,  Sticker  5  reports  tha,t  72,  or  5-5  per  cent., 
had  cancer  ;  while,  according  to  Semmer.e  of  3,525  dogs  examined  at  his 
clinic,  8  per  cent,  were  cancerous. 

1  Bristol  Med.  Chir.  Journ.,  1894,  vol.  xii.,  p.  285. 

2  Deutsche  med.  Woch.,  May  31,  1906,  S.  866. 

3  "  Human  and  Comparative  Pathology,"  1901. 

4  Monats.  f.  prakt.  Thierheilkunde,  1895,  Bd.  vi. 

6  Arch.  f.  klin.  Chir.,  1902,  Bd.  Ixv.,  p.  616  et  scq. 

"Lehrb.  d.  allgem.  Chir.  u.  Operatioiislehre  "  (Moller),  1893. 


CANCER  AND  OTHER  TUMOURS  IN  ANIMALS  95 

These  figures  indicate  that  cancer  is  even  more  prevalent  among  dogs, 
than  among  human  beings. 

All  the  chief  types  and  varieties  of  cancer  met  with  in  mankind,  also 
prevail  among  dogs.  Epithelial  and  sarcomatous  forms  are  common. 
Melanotic  and  myxomatous  varieties  also  occur ;  and  a  form  of  disease, 
"  presenting  the  histological  features  of  rodent  ulcer,"  has  also  been  seen. 
Malignant  tumours  containing  heterotopic  structures — cartilage,  bone 
etc. — are  common.  Leukaemia  also  occurs. 

According  to  Johne,  of  93  tumours  found  post-mortem  in  dogs,  28 
per  cent,  were  sarcomatous. 

Most  of  the  affected  animals  are  domestic  pets  ;  but,  as  previously 
mentioned,  Brooks  has  met  with  sarcoma  of  the  ovary,  in  a  wild  racoon- 
dog,  that  had  been  kept  for  two  years  in  captivity.  Three-quarters  of 
these  animals  were  from  five  to  ten  years  old ;  and  Frohner  says  he  has 
never  seen  a  malignant  tumour  in  a  dog  under  two  years  old. 

Sticker's  analysis  of  738  cases  of  canine  cancer,  shows  that  the  com- 
monest seats  of  the  disease  are  the  mamma  (45  per  cent.),  skin  (21  per 
cent.),  anus  (21  per  cent.),  liver  (3  per  cent.) ;  and,  less  frequently,  the 
kidney,  testis,  penis,  prostate,  eye,  bladder,  vagina,  lung,  thyroid,  ovary 
etc.  Very  remarkable  is  the  great  rarity  of  gastric  cancer,  of  which 
there  was  only  one  instance  ;  the  intestine  provided  not  a  single  example  ; 
and  in  only  two  cases  was  the  uterus  affected. 

Of  the  malignant  mammary  tumours  of  female  dogs,  those  of  the 
epithelial  type  predominate  ;  thus,  of  18  tumours  of  this  kind,  histo- 
logically  examined  by  Cadiot  and  Roger,1  11  were  glandular  epithelio- 
mata,  and  7  were  sarcomata.  Other  interesting  series  of  malignant 
mammary  tumours  have  been  reported  by  Ortschild,2  Cornil  and  Petit,3 
and  MacFadyean.4 

The  usual  type  of  malignant  epithelial  tumour  of  the  dog's  mamma, 
resembles  that  which  is  so  frequent  in  the  breast  of  the  human  female — 
the  acinous  varietv  predominating ;  but  tubular  forms  are  also  met  with, 
which  are  often  associated  with  cysts  and  intra-cystic  papilliferous  growths, 
as  in  humanity.  Acute  and  chronic  varieties  of  the  disease  also  occur, 
and  the  colloid  form  has  also  been  reported  (Gibbes).  Melanotic  mammary 
cancer  has  been  noted  (Crisp  etc.).  In  short,  every  variety  of  mammary 
cancer  that  has  been  discriminated  in  mankind,  may  be  matched  in  the 
dog.  The  hindermost  glands  of  the  series  are  most  prone  to  be  affected. 
Male  dogs  have  relatively  greater  proclivity  to  mammary  cancer,  than  X 
male  humanity. 

In  dogs,  these  malignant  mammary  tumours  are  much  more  fre- 
quently associated  with  gross  heterotopia — cartilaginous,  osseous,  cal- 
careous formations  etc. — than  are  the  corresponding  tumours  of  humanity. 
G.  Petit  5  has  lately  published  a  good  study  of  the  pathology  of  these 
canine  "  mixed  tumours." 

With  regard  to  mammary  sarcomata,  these  are  relatively  of  more 

1  "  Bouchard's  Traitede  Path.  Gen.,"  1895,  t.  i. 

2  Johns  Hopkins  Hosp.  Butt.,  1905,  vol.  xvi.,  p.  185. 

3  Butt,  et  Mem.  Soc.  Anat.  de  Paris,  1905,  t.  Ixxx.,  p.  137. 
*  Journ.  of  Comp.  Path.,  etc.,  1890,  vol.  iii. 

6  Bull.,  etc.,  de  la  Soc.  Anat.  de  Paris,  1906,  No.  5,  p.  373. 


96  THE  NATURAL  HISTORY  OF  CANCER 

^C  frequent  occurrence  in  canine  than  in  human  pathology ;  and  they  also 
are  very  much  more  frequently  associated  with  gross  heterotopia  :  Cadiot 
and  Roger  found  structures  of  this  kind  in  five  out  of  seven  specimens 
examined.  Cystic  and  adenoid  formations  are  as  common  as  in  the 
corresponding  human  tumours ;  and,  as  in  the  latter,  spindle-celled 
elements  predominate.  Alveolar,  melanotic,  and  myxomatous  forms  of 
the  disease  have  also  been  met  with. 

vy  Of  the  numerous  attempts  by  Ortschild,  Gratia,  and  Lienaux,  to 
transmit  these  tumours  by  implantation  to  other  dogs,  all  were  unsuc- 
cessful. 

Of  non-malignant  mammary  tumours,  adenoma,  fibroma,  enchon- 
droma,  osteoma,  papilloma,  and  cystoma  have  been  reported. 

Mammary  fibro-adenomata  are  not  uncommon  in  female  dogs,  and 
Ortschild  has  described  an  instance  of  the  same  malady  in  a  male.  These 
tumours  also  are  fairly  often  associated  with  heterotopic  elements,  such 
as  bone  and  cartilage,  of  which  Rolleston  x  has  studied  examples. 

An  interesting  case  of  villous  papilloma  was  some  time  ago  seen  by 
J.  W.  Sibley2 — "A  multilocular  cystic  tumour,  with  villous  intra-cystic 
growths,  from  the  mamma  of  a  bitch  " — and  Ortschild  has  lately  met 
with  a  similar  case. 

Enchondromatous  and  osteoid  tumours  of  the  mamma  of  female  dogs 
are  comparatively  common,  as  was  long  ago  shown  by  Lebert,  J.  Miiller, 
Virchow,  etc.,  and  modern  instances  of  this  kind  have  been  studied  by 
Adams,  Langlois,  Go  wing  etc. 

Several  examples  of  malignant  disease  of  the  normally  placed  and  of 
the  ectopic  testis  in  dogs  have  been  recorded ;  as  also  of  cancer  super- 
vening after  injuries  ;  thus,  in  a  setter  dog,  Birchmore  saw  sarcoma 
form  after  a  gunshot  wound  of  the  jaw. 

With  regard  to  the  reputed  frequency  of  malignant  disease  in  the 
anus  and  its  vicinity,  which  is  a  special  feature  of  the  neoplastic  pathology 
of  the  dog,  it  is  evident  that  this  matter  requires  further  investigation. 
It  is  already  knoAvn,  however,  that  a  benign  adenomatous  tumour  not 
uncommonly  develops  in  this  vicinity — probably  from  the  circum-anal 
scent-glands — the  exact  nature  of  which  is  still  sub  judice.  These  tumours 
are  circumscribed,  lobulated,  and  easily  shelled  out ;  histologically  they 
consist  of  solid  cylinders  of  epithelial  cells — which  are  sometimes  pig- 
mented — regularly  arranged  in  delicate  vascular  connective  tissue. 
Tumours  of  this  kind  have  been  known  to  recur  after  removal  (Mac- 
Fadyean,3  Wallace  4  etc.) ;  and  it  is  believed  that  one  form  of  malignant 
disease  of  the  anus  arises  from  this  source. 

Anal  cancers  of  the  epidermoidal  type  also  occur. 

G.  Petit5  has  given  an  interesting  account  of  several  cases  of  "  bran- 
chiogenic  "  cancer  of  the  neck  in  dogs. 

Among  the  non-malignant  tumours  met  with  in  these  animals, 
reference  may  be  made  to  fibromyomata  of  the  uterus,  of  which  instances 

Transactions  of  the  Pathological  Society,  London,  1897,  vol    xlviii.,  p    324 

Ibid.,  1858,  vol.  xi.,  p.  460. 

Practitioner,  April,  1899,  p.  460. 

Transactions  of  the  Pathological  Society,  London,  1896,  vol.  xxxviii.,  p.  659. 

Bee.  de  Med.   Vtt.,  1902,  p.  673. 


CANCER  AND  OTHER  TUMOURS  IN  ANIMALS  97 

have  been  reported  by  Keiffer,i  Wagner,2  E.  H.  Williams  and  Hobday  ;3 
and,  in  the  vagina,  similar  tumours  have  been  found  by  Aulton  and  Hob- 
day,4 Leisering  etc. 

Cases  of  ovarian  cystomata  have  also  been  recorded  in  veterinary 
publications  ;  and  a  tumour  of  this  kind  has  been  known  to  attain  a 
weight  of  15  pounds. 

Examples  of  adenoma  of  the  liver  (Schweizer  and  others),  of  the 
kidney  (Jung),  and  polypoid  adenoma  of  the  trachea  (Bid well),  are  also 
on  record. 

Cavernous  angioma  of  the  liver  has  been  seen  by  Petit  and  Virchow. 

A  big  fibrous  tumour,  which  contained  osteoid  deposits,  from  the 
popliteal  space  of  a  large  dog,  is  comprised  in  the  pathological  collection 
of  the  Hunterian  Museum  (No.  800). 

A  large  retro-peritoneal  lipoma  has  been  seen  by  A.  J.  Williams5 
and  by  L.  Hudson.6  Ortschild  7  met  with  a  similar  tumour  in  the  para- 
vaginal  region ;  and  also  in  the  left  pectoral  region — the  latter  animal  being 
also  affected  with  a  malignant  "  mixed  "  tumour  of  the  mamma. 

A  bony  growth,  connected  with  the  cervical  vertebrae,  has  been 
described  by  Viborg. 

Branchial  cysts  have  been  met  with  by  G.  Petit  and  others,  while 
Cathelin  has  seen  a  cyst  connected  with  the  small  intestine,  and  Orts- 
child cystic  hygroma  of  the  shoulder. 

Solid  and  cystic  goitrous  tumours  also  occur,  of  which  many  cases 
have  been  recorded  (Morell  Mackenzie,  Faris  etc.). 

Papillary  cutaneous  excrescences  are  of  common  occurrence  ;  warts 
also  occur  in  the  mouth  and  on  the  foot-pads  of  dogs. 

In  a  subcutaneous  fibroid  swelling,  Lefas  found  included  epidermoidal 
structures  ;  and  Petit  8  has  seen  a  branchial  dermoid  cyst  of  the  neck. 

Several  instances  of  dermoid  hairy  patch  on  the  ocular  conjunctiva 
have  also  been  described  (Dobson,  Taylor  etc.). 

Besides  the  contagious  venereal  growths  previously  referred  to,  dogs 
are  also  prone  to  contagious  papillomata  of  the  mouth,  which  are  trans- 
missible by  artificial  means,  and  resemble  the  "  sublingual  tumour  "  of 
human  nurslings  as  described  by  Riga  and  Fede. 

Dogs  are  comparatively  speaking  but  little  prone  to  tubercle;  yet 
tumour-like  swellings  due  to  this  cause,  to  pseudo-tubercle,  actino- 
mycosis,  streptothrix  and  other  mycotic  infections  are  met  with.  Pick  and 
Poll  have  found  quasi -maMgn&nt  gastric  tumours,  due  to  the  presence  of 
Spiroptera  sanguinolata,  a  small  parasitic  nematoid  worm.  Hydatids 
also  occur.  Examples  of  quasi-malignant  tumours,  caused  by  the 
injection  of  cultures  of  various  microbes,  are  elsewhere  referred  to.9 

In  further  illustration  of  the  subject  of  canine  malignant  tumours, 
the  following  additional  references  may  be  useful  : 

Bull,  de  la  Soc.  Beige  de  Oyn.  et  d'Obstet.,  1900,  t.  x.,  p.  231. 
Cent.  Bl.  f.  attg.  Path.,  etc.,  1905,  vol.  xvi.,  Heft  4. 
Journ.  of  Comp.  Path.,'  1902,  vol.  xv.,  p.  267. 

Veterinary  Journal.  May,  1905,  p.  255.         « 

Veterinarian,  June,  1897,  p.  301. 

Transactions  of  the  Pathological  Society,  London,  1890,  vol.  xli.,  p.  401. 
Op.  tit.  8  Bee.  de  Med.  Vet..  1905,  No.  4,  p.  60. 

Chapter  X. 


98  THE  NATURAL  HISTORY  OF  CANCER 

Six  cases  of  cancer  of  the  breast,  with  inoculation  experiments,  by 
Gratia  and  Lienaux  ;l  cancer  of  mamma  of  a  bitch,  by  Monsarrat  ;2  three 
cases  of  cancer  of  the  axillary  sweat-glands,  by  Creighton  ;3  melanotic 
cancer  of  the  mamma  of  a  terrier  bitch,  with  dissemination  in  the  lungs,  by 
Crisp  ;4  cystic  chondro-sarcoma  of  the  mamma  of  a  bitch,  by  Rolleston  ;5 
cysto-sarcoma  proliferans  of  the  mamma  of  a  greyhound,  with  secondary 
formations  in  the  liver  and  spleen,  and  cystic  disease  of  the  ovaries,  by 
Bertolet  ;6  chondro-osteo-sarcoma  of  the  mamma  of  a  bitch,  by  Virchow  ;7 
cases  of  retro-peritoneal  and  peri-tracheal  sarcoma  in  young  dogs,  by 
Spencer  ;8  cases  of  cystic  myxo-sarcoma  of  the  neck,  by  Creighton  ;9  "  un 
cas  de  chondro-sarcoma  intestinal  generalise  au  poumon,"  by  Petit;10 
cancer  of  prostate,  by  De  Rouville ; u  columnar  epithelioma  of  lung,  by 
Silcock; 12  cystic  sarcoma  of  the  testis  of  an  Italian  greyhound; 13  melanotic 
sarcoma  of  the  immediate  vicinity  of  the  scrotum  in  a  Welsh  terrier,  by 
Leon  ;14  similar  disease  from  the  foot  of  a  dog  ;15  "  myxo-sarcomatodes 
medullare  "  of  the  vagina,  by  Kaschewarowa-Rudnewa ; 16  fibro-spindle- 
celled  sarcoma  of  the  intestine,  with  invasion  of  the  great  omentum  and 
mesenteric  glands,  by  Petit ; 17  sarcoma  of  the  palate  of  an  otter-hound, 
by  Lediard ; 18  osteo-sarcoma  of  the  thigh,  by  G.  Petit  ; 19  sarcoma  of  the 
olfactory  lobe,  by  Marchand  and  Petit  ;20  cases  of  Hodgkin's  disease,  by 
MacFadyean ;  21  lymphomatous  tumours  of  the  spleen,  by  H.  V.  Williams  22 
etc. 

Cat. 

Judging  by  the  comparative  paucity  of  published  cases,  cats  are  much 
less  prone  to  malignant  tumours  than  dogs  ;  but,  according  to  the  records 
of  the  Veterinary  Pathological  Institute  of  Berlin,  this  is  not  so  ;  for  of 
34  cats  there  examined,  2,  or  5-9  per  cent.,  were  thus  affected.  The  usual 
primary  seats  of  the  disease  in  cats  are  the  mamma  and  skin  ;  other  parts 
liable  being  the  lung,  pleura,  liver,  tongue,  ovary,  penis,  eye,  anus,  lip 
etc.  Most  of  the  malignant  forms  of  epithelial  and  connective-tissue 
tumours,  including  the  melanotic,  have  been  reported  in  cats.  Carcino- 
matous  tumours  of  the  mamma  of  the  acinous  and  tubular  types  are  met 

1  "Ann.  de  Med.  Vet.,"  Bruxelles,  1894. 

2  Liverpool  Med.  Chir.  Journ.,  1900,  vol.  xx.,  p.  132. 

3  Transactions  of  the  Med.-Chir.  Society,  London,  1882,  vol.  Ixv.,  p.  53. 
1  Transactions  of  the  Pathological  Society,  London,  1848,  vol.  ii,,  p.  346. 

5  Ibid.,  London,  1897,  vol.  xlviii.,  p.  324. 

6  Philadelphia  Medical  Times,  U.S.,  1872-1873,  vol.  iii.,  p.  315. 
"  Wiirzburger  Verhandl.,"  Bd.  i.,  S.  137. 

8  Transactions  of  the  Pathological  Society,  London,  1891,  vol.  xlii.,  p.  472. 

9  Journal  of  Anatomy,  vol.  xiv.,  p.  292. 

10  Butt.  Soc.  de  Med.  Vet.,  Paris,  1905,  vol  lix  ,  p  283 

11  Butt.  Soc.  Anat.,  Paris,  July,  1896. 

12  Transactions  of  the  Pathological  Society,  London,  1886,  vol.  xxxvii.,  p.  570. 
"  Catalogue  Hunterian  Museum.  Path.  Suppl.,"  p.  71  (No.  4,235). 

14  British  Medical  Journal,  1899,  vol.  ii.,  p.  1046. 

1  "  Catalogue  Hunterian  Museum,"  Path.  Series,  No.  469A. 
18  Arch.  f.  path.  Anat.,  1872,  Bd.  liv.,  S.  73. 

17  Butt.  Soc.  Anat.,  Paris,  1899,  p.  487. 

18  Transactions  of  the  Pathological  Society,  London,  1888,  vol.  xxxix.,  p.  458. 

19  Ike.  de  Med.  Vet.,  February,  1906,  p.  81. 

20  Butt.  Soc.  Anat.,  Paris,  1906,  No.  5,  p.  397. 

21  Journ.  of  Comp.  Path.,  etc.,  1903,  vol.  xvi.,  p.  379. 
Journal  of  Medical  Eesearch,  1902,  vol.  vii.,  p.  408. 


CANCER  AND  OTHER  TUMOURS  IN  ANIMALS  99 

with  ;  among  those  who  have  recently  studied  specimens  of  this  kind 
are  Petit,1  Leiden,2  Spencer,3  and  Eva  Field.4 

The  last  named  has  also  described  an  example  of  cystic  round-celled 
sarcoma  of  the  subcutaneous  tissue  below  the  ear  ;  and  Breton  and  Petit 5 
a  case  of  intra-ocular  sarcoma  of  the  globe  of  the  eye  ;  while  Stroud  6  has 
met  with  sarcoma  of  the  ovaries  and  pelvis. 

There  is  a  specimen  of  cancellous  exostosis  of  the  lower  jaw  in  the 
Hunterian  Museum  ;  7  and  a  similar  formation  connected  with  the  upper 
part  of  the  femur  is  in  Guy's  Hospital  Museum.  The  Hunterian  Museum 
also  exhibits  the  omentum  of  a  cat  studded  with  small,  stalked,  fibro-fatty 
outgrowths  ;  and  angiomata  of  the  liver  has  also  been  noticed. 

An  example  of  sublingual  ranula  has  been  seen  by  Ridler  and  Hobday,8 
and  the  same  authors  have  also  reported  a  case  of  nasal  polypus. 

Like  other  carnivorous  animals,  cats  are  but  little  prone  to  tubercle. 


Horse. 

Malignant  tumours  in  horses  are  decidedly  rare,  for,  according  to 
Sticker,  of  215,037  of  these  animals  under  treatment  at  the  Berlin 
"  Hochschule  "  Veterinary  Clinic,  only  103  were  thus  affected,  or  0-046  per 
cent.  However,  many  cases  are  on  record  in  the  veterinary  journals  ;  and 
of  Sticker's  1,170  tabulated  cases,  318  were  in  horses. 

The  commonest  primary  seats  of  the  disease  are  :  —  the  antrum  and  the 
adjacent  naso-oral  cavities9  (16  per  cent.),  the  penis  (16  per  cent.), 
kidney  (9  per  cent.),  skin  (7  per  cent.),  lung  and  pleura  (5-6  per  cent.), 
bladder  10  (4-4  per  cent.),  testis  (4  per  cent.),  eye  (4-4  per  cent.)  ;  and  in 
lesser  degrees  of  frequency,  the  vulva,  gum,  stomach,  anus,  mamma,11 
uterus,  vagina,  intestine,  ovary,  larynx,  tail  12  etc. 

Not  a  single  example  of  malignant  disease  of  the  tongue  is  comprised 
in  the  356  cases  in  horses,  tabulated  by  Sticker,  MacFadyean,  Bashford, 
Cadiot  and  Roger  ;  and  it  is  noticeable  that  gastric,  intestinal,  and  uterine 
malignant  tumours,  are  exceedingly  rare  in  these  animals. 

The  melanotic  form  of  tumour  disease  is  of  common  occurrence  in 
horses,  especially  in  those  of  white,  grey,  roan,  and  dun  tints  ;  but  even 
the  black  varieties  are  not  exempt.  Its  commonest  seats  are  the  anus, 
root  of  the  tail,  external  genitals,  skin  etc.  Most  formations  of  this 
kind  are  of  a  chronic  nature,  and  comparatively  benign  —  these  are 
described  by  Cornil  and  Trasbot  13  as  fibromata  ;  but  occasionally  they 

Butt.,  etc.,  Soc.  Anat.,  Paris,  1905,  t.  Ixxx.,  p.  137. 

Zeits.  f.  klin.  Med.,  1904,  vol.  Hi.,  p.  409. 

Transactions  of  the  Pathological  Society,  London,  1890,  vol.  xli.,  p.  400. 

Journal  of  American  Medical  Association,  December  29,  1904,  p.  983. 


Pec.  de  Med.  Vet.,  Paris,  1902,  t.  ix.,  p.  38 

17. 

talogue,"  vol.  iii.,  p.  12. 
Journal,  June,  1905,  p.  3 
,  the  cheek  being  the  pa 
vol.  xvi.,  p.  161. 


eternary    ourna,    une,  1,  p.         . 

"  Path.  Catalogue,"  vol.  iii.,  p.  12. 

Veterinary  Journal,  June,  1905,  p.  333. 

9  For  a  case,  the  cheek  being  the  part  affected,  vide  Journ.  of  Comp.  Path.,  1903, 
xvi.,  p.  161. 

10  Case  by  MacFadyean,  Journ.  of  Comp.  Path.,  1902,  vol.  xv.,  p.  148. 

11  For  a  case,  vide  Journ.  of  Comp.  Path.,  1903,  vol.  xvi.,  p.  161. 

12  Case  by  MacFadyean,  Journ.  of  Comp.  Path.,  1902,  vol.  xv.,  p.  148. 

13  "  De  la  Melanose,"  1868. 

7—2 


100  THE  NATURAL  HISTORY  OF  CANCER 

manifest  all  the  properties  of  malignancy,  with  widespread  dissemina- 
tion, and  are  then  generally  described  as  being  of  sarcomatous  structure, 
spindle  cells  predominating.  Melanotic  tumours  sometimes  attain  great 
size,  weighing  as  much  as  from  20  to  60  pounds  ;  and  some  remarkable 
instances  of  their  heredity  are  cited  by  Virchow.1  Lebert 2  mentions  a 
case  in  which  a  black  tumour,  that  had  long  existed  under  the  root  of  the 
tail  at  length  became  generalized,  thousands  of  small  tumours  forming  in 
the  lungs,  liver,  peritoneum,  pericardium,  spleen,  and  in  many  other 
parts.  The  Royal  College  of  Surgeons  Museum  in  London  contains  two 
interesting  specimens  of  this  malady  prepared  by  Hunter  : 

1.  No.  290,  Pathological  Series  :  "  A  section  of  the  tail  of  a  horse,  and 
of  a  large,  lobulated,  soft,  pale  brown  and  black  tumour,  embedded  deeply 
in  its  substance,  and  projecting  in  lobes  and  lobules  on  its  surface." 

2.  No.  291,  Pathological  Series  :  "  Melanotic  tumour  removed  from 
the  neck  of  a  horse.     It  is  black  throughout,  firm,  lobulated,  and  loosely 
encapsulated  (10  by  5  inches).     It  was  removed  by  Hunter  from  the 
inner  side  of  the  jugular  vein,  which  passed  over  it." 

A  good  example  of  the  malignant  form  of  melanosis,  with  widespread 
dissemination,  has  been  described  by  Hutchinson.3  Bloodgood  4  has  met 
with  the  same  disease  in  the  liver,  and  G.  Petit 5  within  the  spinal  canal. 

A  specimen  of  intra-ocular  melanoma,  which  filled  the  whole  globe, 
and  had  involved  also  the  orbit,  is  contained  in  the  Hunterian  Museum 
(No.  2,259,  Pathological  Series). 

Epidermoidal  cancer  of  the  membrana  nictitans,  with  dissemination, 
has  been  described  by  MacFadyean ;  6  and  instances  of  epidermoidal 
cancer  of  the  ocular  conjunctiva  by  Petit  and  Coquot,7  and  by  Taylor.8 

Malignant  tumours  are  of  specially  frequent  occurrence  in  gelded 
animals  ;  thus,  of  seven  examples  of  epidermoidal  cancer  of  the  penis 
in  MacFadyean' s  list,  all  were  from  geldings. 

Instances  of  epithelioma  of  the  penis  have  been  studied  by  Patteson,9 
and  Webber,10  of  the  vulva  by  Petit,11  and  of  the  vagina  by  Bashford.12 

Of  128  tumours  found  post-mortem  in  the  horse,  Johne  found  that 
60,  or  47  per  cent.,  were  sarcomatous. 

An  example  of  "  alveolar  sarcoma  "  of  the  upper  jaw  has  been  pub- 
lished by  Pike  ; 13  and  veterinary  museums  generally  contain  specimens  of 
"  spina  ventosa  "  of  this  locality,  most  of  which  are  due  to  sarcomatous 
tumours.  Malignant  epithelial  tumours,  mostly  of  the  epidermoidal 
type,  also  arise  from  the  antrum. 

, l  "  Path,  des  Tumeurs,"  1869,  t.  ii.,  p.  236. 

"  Traite  des  Mai.  Cancereuses,"  p.  159. 
3  Archives  of  Surgery,  1890,  vol.  iv.,  p.  48. 
*  Johns  Hopkins  Hospital  Bull.,  June,  1905,  p.  239. 

5  Bull,  et  mtm.  Soc.  Anat.,  Paris,  1905,  No.  5,  p.  382. 

6  Journ.  of  Comp.  Path.,  1904,  vol.  xvii.,  p.  352. 

7  Bee.  de  Mid.   Vet.,  1905,  t.  Ixxxii.,  No.  1,  p.  10,  with  excellent  clinical  and  histo- 
logical  figures. 

8  Royal  London  Ophthalmic  Hospital  Reports,  1876,  vol.  ix.,  p.  74. 

9  Illustrated  Medical  News,  December,  1888,  p  220 

10  British  MedicalJournal,  1899,  vol.  ii.,  p.  882. 

11  Bee.  de  Med.  Vet.,  Paris,  1902,  vol.  ix.,  p.  118. 

12  Proceedings  of  the  Royal  Society,  London,  1904,  vol.  Ixxiii. 

13  British  Medical  Journal,  1896,  vol.  i.,  p.  989. 


CANCER  AND  OTHER  TUMOURS  IN  ANIMALS  101 

Sarcomatous  tumours  of  the  lower  jaw  have  been  reported  by  Lediard * 
and  Waldmann  ;2  while  many  examples  of  "  spina  ventosa  "  of  this  bone 
are  to  be  found  in  veterinary  museums. 

Actinomycetic  tumours  of  the  naso-oral  region,  which  are  of  common 
occurrence  in  horses,  require  to  be  discriminated  from  malignant  tumours 
of  this  vicinity,  which  they  often  closely  simulate. 

Sarcomatous  tumours  growing  from  the  ribs,  ulna,  etc.,  have  also 
been  met  with. 

Several  cases  of  leukaemia,  and  of  intra-thoracic  lumphadenoid  disease 
have  been  recorded  (Petit,  Weil  etc.).  * 

Malignant  disease  of  the  retained  testis  has  been  seen  by  Axe  3  and 
others;  while  several  cases  of  ossifying  chondro-sarcoma,  and  of  carcinoma, 
of  this  organ  are  on  record  (Gamgee  etc.). 

Examples  of  intra-ocular  and  orbital  sarcoma  are  referred  to  by  Axe ; 
and  there  is  a  specimen  of  this  kind  in  Guy's  Hospital  Museum. 

Several  specimens  of  mammary  carcinoma  in  the  mare  have  been  met 
with  (MacFadyean,  Cadiot  and  Roger  etc.)  ;  and  a  large  cystic  fibro- 
adenomatous  tumour  of  this  part  in  a  mare,  which  comprised  ossifying 
and  chondromatous  structures,  and  was  of  "a  quasi-carcinomatous 
nature  in  some  parts,"  has  been  described  by  Scott.4 

Eight  instances  of  cancer  of  the  uterus,  7  of  the  vagina,  4  of  the 
ovary,  and  8  of  the  stomach,  are  included  among  Sticker's  318  malignant 
horse  tumours  ;  and  Bland-Sutton  has  seen  2  cases  of  uterine  sarcoma. 

An  example  of  ulcerated  cancer  of  the  skin  behind  the  ear,  which  was 
ascribed  to  the  irritation  of  a  papillary  excrescence  by  the  bridle,  has 
been  met  with  by  Birchmore  ;  5  and  Woods  Hutchinson  has  seen  sarcoma 
of  the  lip  of  a  horse. 

I  have  previously  referred  to  Penberthy's  case  of  congenital  sarcoma 
of  a  foal. 

-Judging  by  the  numerous  specimens  of  exostoses  and  osteomata  con- 
tained in  the  chief  museums,  horses  must  be  very  prone  to  these  forma- 
tions. I  have  references  of  growths  of  this  kind  connected  with  the 
spine,  pelvic  bones,  inferior  maxilla,  ribs,  sternum,  scapula,  humerus, 
cannon  bone,  gluteal  aponeurosis,  palate,  nasal  septum,  etc. 

Ivory  exostoses  of  the  skull  bones,  like  those  met  with  in  human 
pathology,  also  occur  ;  and  a  tumour  of  this  kind,  as  big  as  a  man's  fist, 
has  been  known  to  have  been  shed  spontaneously  from  the  nostril  of  a 
horse.  Loose  bony  and  cartilaginous  tumours  have  also  been  found  in 
the  knee-joint. 

Many  instances  of  exostoses  due  to  ossification  of  the  tendons  of 
muscles,  have  also  been  met  with.6 

Some  remarkable  instances  of  odontomata  and  dentigerous  so-called 
"  cranial  dermoids  "  have  been  described  by  Broca,7  chiefly  from  speci- 

Transactions  of  the  Pathological  Society,  London,  1884,  vol.  xxxv.,  p.  468. 

Zeits.f.  Thier-med.,  1899,  Bd.  iii.,  S.  199. 

Veterinarian,  vol.  xxv.,  p.  262. 

Veterinarian,  July,  1895,  p.  462. 

New  York  Medical  Journal,  1883,  vol.  xxxviii.,  p.  659. 

For  references  to  cases,  vide  Barrier,  Pec.  de  Med.  Vet.,  1905,  t.  Ixxxii.,  No.  6,  p.  115. 

"  Traitedes  Tumeurs,"  1869,  t.  ii.,  chap.  x. 


102  THE  NATURAL  HISTORY  OF  CAXCER 

mens  in  the  celebrated  Alfort  and  other  veterinary  museums.  Aberrant 
teeth  in  horses  have  also  been  noted  in  the  palate  bone,  and  more  rarely 
in  the  petrous  bone  ;  and  probably  some  of  these  odontomata  arise  from 
redundant,  aberrant  tooth  germs.1 

A  peculiar  kind  of  symmetrical  hyperostosis  of  the  maxillary  bones 
of  West  African  horses  and  mules — recalling  the  affection  known  as 
"  goundrou,"  which  occurs  among  the  negroes  of  the  Ivory  Coast — has 
been  studied  by  Zieman  2  ;  and  Ridewood3  exhibited  not  long  ago  at  the 
Linnean  Society  a  specimen  of  a  similar  condition,  bu  the  regarded  the 
symmetrical  bony  bosses  as  indications  of  a  pair  of  rudimentary  horns  ! 

Horses  are  liable  to  fibrous  and  papillary  growths ;  while  sebaceous 
cysts  and  horny  excrescences  have  also  been  noted. 

Virchow,4  R.  W.  Smith,5  A.  Thomson,6  and  De  Boinville,?  have 
reported  instances  of  multiple  fibro-neuromata  in  horses  and  other 
domesticated  animals. 

In  the  body  of  an  old  mare,  sent  to  the  Clifton  Zoo  to  be  slaughtered 
as  food  for  the  carnivora,  Harrison  8  found  an  enormous  fibro-myomatous 
tumour  of  the  uterus  ;  and  Virchow  had  previously  called  attention  to 
tumours  of  this  kind,  in  the  uterus  and  vagina  of  horses  and  other  animals. 

A  large  fibro-myomatous  tumour  of  the  duodenum  of  a  mare,  which 
had  caused  fatal  intestinal  obstruction,  has  been  described  by  Cadeac  9 
— extensive  areas  of  the  tumour  being  in  a  state  of  fatty  degeneration. 

A  good  many  instances  of  polypoid  adenomatous  tumours  of  the 
intestine  projecting  within  the  gut,  have  also  been  found.  An  ossified 
tumour  of  this  kind  of  the  caecum,  has  been  reported  by  G.  Petit,10  who  has 
also  met  with  a  similar  growth  in  the  rectum,  which  was  undergoing 
calcification ; 1X  and  peri-anal  adenomatous  tumours  also  occur. 

Several  instances  of  pedunculated  so-called  fatty  tumours  connected 
with  the  small  intestine,  which  had  caused  fatal  intestinal  obstruction, 
have  also  been  recorded  in  veterinary  publications ;  and  these  tumours  are 
generally  referred  to  as  overgrown  appendices  epiploicse  ;  but,  in  the  light 
of  Cadeac's  case,  some  of  them  may  be  otherwise  derived. 

To  such  sources  as  the  foregoing,  many  of  the  foreign  bodies — often  of 
considerable  size — found  free  in  the  peritoneal  cavity,  may  be  referred. 

Large  intra-abdominal  fatty  tumours  have  also  been  met  with  in 
horses  and  other  domesticated  animals  (Fiirstenburg).  Hobday12  has 
seen  lipoma  in  the  undescended  testis,  which  specimen  is  now  preserved 
in  the  Hunterian  Museum ;  and  MacFadyean  has  seen  two  examples  of 
subcutaneous  lipoma  of  the  fore-leg. 

1  Ridler,  "  Dentigerous  cyst  in  the  vicinity  of  the  ear  of  a  Mare,  which  contained 
two  odontomatous  masses,  one  of  great  size,"  Journ.  of  Comp.  Path.,  etc..  1902,  vol.  xv., 
p.  266  ;  also  Hobday,  ibid.,  vol.  xii.,  p.  174. 

2  Journal  of  Tropical  Medicine,  London,  May  1,  1905,  p.  135. 

3  Proceedings  of  the  Linnean  Society,  October,  1904,  p.  i. 
"  Path,  des  Tumeurs,"  t.  iii.,  p.  496. 

"  Sydenham  Society's  Atlas.  Illust.  Path.,"  fasc.  xi. 

6  '•Neuroma  and  Neuro-fibromatosis."     Edinburgh,  1900. 

7  Veterinary  Journal,  March.  1905.  p.  130. 

8  Bristol  Med.  Chir.  Journ.,  1894,  vol.  xii.,  p.  288. 

9  tec.  de  Med.  Vet.,  March  15,  1885. 

10  Butt,  et  mem.  Soc.  Anat.,  Paris,  January,  1902. 

11  Rec.  de  Med.  Vet.,  1905,  No.  6,  p.  122. 

12  Transactions  of  the  Pathological  Society,  London,  1906. 


CANCER  AND  OTHER  TUMOURS  IN  ANIMALS  103 

Ovarian  and  parovarian  cysts  are  not  unknown  ;  and  a  tumour  of  this 
kind  has  been  reported,  which  weighed  as  much  as  84  pounds. 

Ovarian  dermoids  are  also  found;  and,  in  a  case  of  this  kind  by  Pollock,1 
in  addition  to  piliferous  pigmented  skin,  the  tumour  contained  cartila- 
ginous and  ossifying  structures. 

Tumours  of  somewhat  similar  composition  have  also  often  been  found 
in  connexion  with  the  testis,  especially  during  castration.2 

Dermoid  cysts,  sometimes  containing  teeth,  have  been  met  with  in 
the  temporal,  petrous,  and  sphenoid  regions  ;  while  Leblanc  3  has  seen  an 
intra-cranial  piliferous  dermoid. 

Horn-like  cutaneous  outgrowths  often  occur  in  horses. 

Spencer4  has  reported  a  case  of  polycystic  disease  of  both  kidneys,  so 
diffused  that  hardly  any  normal  renal  structure  could  be  seen. 

Cysts  of  the  unobliterated  urachus  have  been  met  with  in  horses, 
cows,  pigs,  etc. 

Horses  are  singularly  liable  to  the  formation  of  large  intra-cerebral 
tumours,  in  connexion  with  the  choroid  plexuses — the  so-called  "  psam- 
moma  ";  or,  by  reason  of  their  richness  in  cholesterine,  "  cholesteatoma," 
of  which  examples  have  been  reported  by  McCarthy,5  Saundby,6  Mac- 
Fadyean  7  etc. 

A  unique  case  of  rhabdo-myoma  of  the  subcutaneous  shoulder  region, 
has  been  described  by  Monod,8  in  which  the  tumour  was  attached  by  a 
long  thin  pedicle  to  the  scapula. 

Horses,  mules,  and  asses  are  also  subject  to  goitrous  thyroid  tumours. 

Malignant  tumours  occur  in  mules  and  asses  ;  but  I  have  found  very 
few  cases  of  this  kind  on  record. 

An  instance  of  round  and  spindle-celled  sarcoma  of  the  lower  lip  of 
a  mule,  following  injury  by  the  bit,  has  been  reported  by  Birchmore  ;  and 
these  animals,  as  well  as  asses,  are  liable  to  melanosis. 

In  the  ass,  cases  of  sarcoma  of  the  colon,  testis,  and  of  the  lung 
(chondro-sarcoma)  have  also  been  published. 

Pseudo-plasms  consequent  on  actinomycosis,  aspergillosis,  bothryo- 
mycosis,  and  other  parasitic  affections,  are  of  not  uncommon  occurrence 
in  horses  ;  and  Hutchinson 9  has  described  an  example  of  intra-ocular 
hydatid  cyst.  Tuberculosis  occurs,  but  it  is  not  common.  Tumour-like 
swellings  in  the  walls  of  the  stomach,  due  to  oestrus  larva,  have  also  been 
noted.  A  tumour-like  lesion  of  the  lung,  due  to  blastomycetic  infection, 
has  been  reported  by  Frothingham  ;10  a  mycotic  maxillary  tumour  by 
Foulerton,u  and  a  fibroid  tumour-like  mass  of  the  spermatic  cord,  due  to 
bothryomycosis,  by  Wolstenholme.12 

1  Transactions  of  the  Obstetric  Society,  London,  1890,  vol.  xxxi. 

2  Vide  Journ.  of  Comp.  Path.,  etc.,  1903,  vol.  xvi.,  p.  127 ;  ibid.,  1905;  April,  p.  210; 
and  Transactions  of  the  Pathological  Society,  London,  1906. 

3  Bee.  de  lied.  Vet.,  t.  viii.,  p.  342. 

4  Transactions  of  the  Pathological  Society,  London,  1890,  vol.  xli.,  p.  397. 

5  Univ.  Pennsylvania  Med.  Butt.,  U.S.,  October,  1904.  p.  265. 

6  British  Medical  Journal,  1882,  vol.  ii.,  p.  896. 

7  Journ.  of  Comp.  Path.,  etc.,  1902,  vol.  xv.,  p.  162. 

8  Rec.  de  MM.   Vet..  June  30,  1902. 

9  Transactions  of  the  Pathological  Society,  London,  1857,  vol.  viii.,  p.  413. 

10  Journal  of  Medical  Research,  Boston.  U.S..  1902,  vol.  viii.,  p.  31. 

11  Transactions  of  the  Pathological  Society.  London,  1900,  vol.  li.,  p.  51. 

12  British  Medical  Journal,  1902,  vol.  i.,  p.  84. 


104  THE  NATURAL  HISTORY  OF  CANCER 


Ox. 

In  bovine  animals,  according  to  Sticker,  malignant  tumours  are  very 
uncommon ;  for  of  5,795,  only  7  were  thus  affected. 

The  same  authority  states  that  their  commonest  seat  is  the  uterus 
(16  in  74  cases) ;  but  I  find  that  the  liver1  and  stomach  head  the  lists  of 
most  pathologists.  Other  parts  liable  to  be  affected  are  : — the  kidney, 
bladder,  ovary,  lung,  eye,  skin,  vulva,  penis,  vagina,  adrenal  etc. — all 
the  chief  varieties  of  malignant  disease  being  represented. 

In  the  Chicago  stockyards,  Jobson  and  Loeb  2  found  that  cancer  of 
the  ocular  conjunctiva  was  the  commonest  form  ;  and  cancer  of  the  vulva 
was  also  met  with. 

There  is  a  specimen  of  cancer  of  the  rectum  in  the  Hunterian  Museum 
(No.  1,265,  Pathological  Series) ;  and  also  of  melanoma  of  a  white  cow's 
udder  (No.  469,  Pathological  Series). 

Cadeac3  has  met  with  melanotic  fibroma  of  the  buttock  of  a  cow 
seven  years  old,  and  he  refers  to  other  cases  of  the  kind  ;  the  Hunterian 
Museum  contains  a  melanotic  tumour,  the  size  of  a  man's  fist,  which  was 
removed  from  near  the  knee  of  a  young  cow  ;  and  Bashford  4  has  seen 
cases  of  melanotic  sarcoma  of  the  perineum  and  thigh  of  young  cows. 

Hamburger5  has  described  "  chondro-fibro-melano-sarcoma  "  of  the 
pleura  and  diaphragm  of  a  cow;  and  Pike6  "  alveolar  sarcoma "  of  the 
submaxillary  region  of  a  young  bullock. 

Examples  of  "  spina  ventosa"  of  the  superior  and  inferior  maxilla, 
of  the  metacarpal  and  pastern  bones,  etc.,  are  to  be  found  in  veterinary 
museums. 

Exostoses  and  osteomas  are  as  common  in  bovine  animals  as  in 
horses  ;  in  the  Hunterian  Museum  (No.  3,216,  Pathological  Series)  is  a 
large  ivory  ex ostosis  from  the  frontal  bone  of  an  ox,  which  weighs  16  pounds, 
and  measures  8£  inches  in  diameter.  Odontomata  also  occur. 

On  examining  the  body  of  an  apparently  healthy  cow,  Colin7  found 
the  nerves  studded  with  innumerable  tumours  (neuro-fibromata) ,  mostly 
of  small  size  ;  but,  in  connexion  with  the  solar  plexus,  there  was  a  large 
tumour,  which  weighed  5  pounds  :  other  cases  of  this  kind  are  referred 
to  by  Virchow. 

"  Fibroid  "  tumours  of  the  uterus,  vagina,  and  submucosa  of  the 
stomach  occur  ;  and  in  the  Hunterian  Museum  (No.  194,  Pathological 
Series)  is  an  encapsuled  bilobed  tumour,  of  fatty  appearance,  attached 
by  a  long  pedicle  to  the  intestine  of  an  ox. 

Cutaneous  horns  are  sometimes  met  with  ;  in  the  Hunterian  Museum 
there  is  a  specimen  of  a  large  growth  of  this  kind  from  the  skin  of  the 

1  For  note  as  to  the  frequency  of  "  adeno-carcinoma  "  of  the  liver  in  Irish  cows,  vide 
Trotter  (Journ.  of    Comp.  Path.,   1904,  vol.  xvii.,  p.   127).      May  not  many  of  these 
tumours  be  due  to  some  as  yet  undiscriminated  microbic  infection  ?     This  is  suggested 
by  the  undue  incidence  of  the  disease  in  the  liver. 

2  Arch.  f.  klin.  Chir.,  Bd.  Ixx.,  1903,  p.  845  ;  also  Medicine,  April,  1900. 

3  Bee.  de  Med.  Vet.,  March  15,  1885. 

4  Scientific  Report  of  the  Cancer  Research  Fund,  No.  2,  1905. 

5  Arch.  f.  path.  Anat.,  Bd.  cxvii.,  p.  427. 

6  British  Medical  Journal,  1896,  vol.  i.,  p.  989. 

7  Bee.  de  Med.  Vet.,  t.  viii.,  p.  947. 


CANCER  AND  OTHER  TUMOURS  IN  ANIMALS  105 

forehead  of  an  ox  :  similar  formations  have  been  seen  on  the  neck  and 
elsewhere. 

Ebinger1  has  recorded  an  instance  of  lipoma,  found  within  the  spinal 
canal  of  a  cow. 

Papillary  growths  of  the  penis,  vagina,2  gall-bladder,3  tongue,  osso- 
phagus,  etc.,  have  been  met  with. 

Mammary  adenomata  and  fibromata  are  fairly  common. 

Multiple  polypi  of  the  mucosa  of  the  small  intestine  of  a  cow  have 
been  reported  by  MacFadyean.4 

Ovarian  cystoma  are  not  very  exceptional,  often  attaining  great  size  ; 
an  example  of  multiple  myomata  of  the  uterus  has  been  described  by 
Spreull,5  in  which  there  were  fifteen  large  tumours — each  about  the  size 
of  a  melon — and  many  small  ones. 

Cysts  of  abdominal,  renal,  intestinal,  vaginal,  and  vesical  location 
have  also  been  reported  ;  and  hydatids  are  common. 

Specimens  of  dermoid  cysts  containing  hairs,  teeth,  etc.,  are  to  be 
found  in  the  Hunterian  and  other  museums  ;  and  Windle  6  has  met  with 
a  teratoma  of  the  sphenoid  in  a  calf. 

In  the  Hunterian  Museum  (No.  161,  Pathological  Series)  is  a  dermoid 
cyst  from  the  shoulder  of  a  cow  with  six  legs  ;  the  cyst  contained  hairs, 
fatty,  and  calcareous  matter.  An  instance  of  a  branchial  dermoid  cyst 
of  the  lower  part  of  the  neck  by  Trotter,?  is  also  on  record. 

Bovine  animals  are  specially  prone  to  tubercle,  as  well  as  to  the  w' 
same  kinds  of  pseudo-plasms  as  horses. 

Pig. 

There  is  a  consensus  of  opinion  among  veterinarians,  which  finds 
some  support  in  the  paucity  of  recorded  cases,  that  malignant  tumours 
are  of  rare  occurrence  in  swine.  Of  over  100  malignant  tumours  examined 
by  MacFadyean,  Cadiot,  and  Roger,  there  was  not  a  single  example  from 
a  pig ;  and  Sticker's  list  of  1,170  similar  tumours  comprises  only  12  from 
this  animal.  Gaylord  and  Zink 8  found  4  malignant  tumours  among 
about  2,000  swine,  mostly  young,  slaughtered  at  Buffalo.  Judging  by 
recorded  cases,  the  kidney,  skin,  and  liver  are  the  commonest  seats  of 
initial  manifestation.  Other  localities  noted  are  intra- abdominal,  lymph- 
glands,  submaxillary  gland,  parotid,  testis,  penis,  maxillary  bones, 
vertebrae  etc. 

Hamburger9  has  made  detailed  study  of  a  case  of  kidney  sarcoma  ; 
and  Bashford  has  met  with  mixed-celled  sarcoma  of  the  submaxillary 
gland.  Several  cases  of  Hodgkin's  disease  in  swine  have  also  been 
reported. 

1  Veterinary  Journal,  1902,  p.  170. 

2  For  report  of  a  large  condylomatous  tumour  of  the  vagina  of  a  young  cow.  vide 
Waghorn,   Veterinary  Journal,  May,  1905,  p.  253. 

3  Virchow  has  described  and  figured  a  case  ("  Path,  des  Tumeurs,"  t.  i.,  1867,  p.  337). 

4  Journ.  of  Comp.  Path.,  etc.,  1902,  vol.  xv.,  p.  155. 

5  Journ.  of  Comp.  Anat.,  etc.,  1904,  vol.  xvii.,  p.  64. 

6  Journ.  of  Anatomy,  vol.  xxii.,  p.  420. 

7  Journ.  of  Comp.  Path.,  etc.,  1903,  vol.  xvi.,  p.  55. 

8  Clinical  Journal,  June  11,  1902,  p.  125. 

9  Arch.  f.  path.  Anat.,  Bd.  cxvii.,  S.  422. 


106  THE  NATURAL  HISTORY  OF  CAXCER 

Published  records  of  non-malignant  tumours  in  swine  are  even  more 
scanty,  than  those  concerning  malignant  tumours.  "Fibroids"  have 
been  discriminated  in  the  uterus  and  vagina,  and  in  the  latter  organ 
Wolffian  duct  cysts  occasionally  occur.  Papillomatous  tumours  of  the 
intestine,  exostosis  of  the  ischium,  bothryomycetic  pseudo-plasms, 
hydatid  cysts  of  the  liver,  etc.,  and  goitrous  tumours  of  the  thyroid,  have 
also  been  noted. 

Swine  are  but  moderately  prone  to  tubercle.  ^ 

Sheep. 

Sheep  are  unquestionably  much  less  prone  to  malignant  tumours 
than  any  of  our  common  domesticated  animals  ;  indeed,  Sticker's  list 
of  1,170  of  these  tumours,  comprises  only  7  from  sheep  :  of  6,800  sheep 
slaughtered  during  four  years  at  Hah' fax,  only  one  instance  of  malignant 
tumour  was  found.1 

Of  the  few  recorded  cases,  in  the  great  majority  the  liver  was  the  site 
of  initial  manifestation  ;  other  parts  affected  being  the  maxillary  bones, 
eye,  orbit,  lung  etc. 

Examples  of  intra-ocular  and  orbital  malignant  tumours  have  been 
described  by  Axe  and  others ;  and  a  specimen  of  this  kind  is  in  Guy's 
Hospital  Museum. 

An  example  of  "  spina  ventosa  "  of  the  inferior  maxilla,  owing  to  the 
growth  of  central  sarcoma,  is  preserved  in  the  Edinburgh  Anatomical 
and  Pathological  Museum  (No.  6  :  487) ;  and  the  Cancer  Research  Staff  has 
lately  examined  a  specimen  of  ossifying  sarcoma  of  the  same  bone. 

Sharp2  has  published  an  account  of  a  large  cystic  myxoma  attached 
to  the  colon. 

With  regard  to  non-malignant  tumours,  very  few  modern  instances 
have  been  recorded.  Ovarian  cystomata  occur,  a  specimen  weighing 
7  pounds  having  been  met  with.  Poly  cystic  disease  of  the  kidneys  has 
also  been  recognized,  and  there  is  a  specimen  of  this  kind  in  the  Hun- 
terian  Museum.  In  this  connexion,  it  is  of  interest  to  note  the  occur- 
rence of  polycystic  disease,  affecting  concomitantly  several  internal  organs 
as  well  as  the  kidneys — e.g.,  liver,  lungs,  and  even  the  cardiac  musculature, 
of  which  Cruveilhier  has  reported  examples.  Eve3  has  seen  a  cyst,  con- 
nected with  the  undescended  testis  of  a  sheep  with  hermaphroditic  mal- 
formation. Fatty  tumours  are  stated  to  be  met  with  in  sheep,  but  I 
cannot  cite  a  modern  instance,  unless  the  curious  case  described  by 
Paget,4  be  so  regarded.  Here  a  mass  of  fatty  outgrowths  surrounded 
the  outside  of  the  heart,  and  processes  were  embedded  in  its  substance, 
some  of  which  even  projected  into  its  cavities. 

Papillary  growths  and  cutaneous  horny  excrescences  are  met  with  : 
some  remarkable  examples  of  the  latter  have  been  recorded,  e.g.,  a  horn 
connected  with  the  throat,  weighing  26  pounds,  and  a  similar  formation 
of  the  flank  3  feet  in  length. 

1  JY  F.  Hodgkinson.  Journ.  of  Gotnp.  Path.,  etc.,  1903,  vol.  xvi.,  p.  269  ;  a  case  of 
cystic  cancer  of  the  liver.  2  Journal  of  Anatomy,  1896,  vol.  xxx.,  p.  559. 

3  Transactions  of  the  Pathological  Society,  London,  1889,  vol.  xl.,  p.  463. 
"  Surgical  Pathology,"  1853,  vol.  ii.,  p.  93. 


CANCER  AND  OTHER  TUMOURS  IN  ANIMALS  107 

Many  instances  of  dermoid  cysts  are  preserved  in  museums.  A 
piliferous  formation  of  this  kind,  replacing  one  of  the  kidneys,  of  which 
there  was  no  trace,  is  in  the  Hunterian  Museum  ;  it  contained  masses 
of  rolled-up  wool,  oily  and  fatty  matters  (No.  1,904,  Pathological  Series) : 
another  specimen,  in  the  Hunterian  Museum  at  Glasgow,1  is  described 
as :  "  cyst  from  a  sheep's  leg ;  a  long  spindle-shaped  cyst,  with  fairly 
thick  walls,  covered  internally  with  fine  hairs ;  it  is  filled  with  balls  of 
tightly  compressed  hairs,  which  had  grown  from  its  surface,  shed,  and 
accumulated  gradually."  Other  examples  of  these  formations  are  con- 
tained in  the  London  Hunterian  Museum  ;  and  two  tumours  of  this  kind, 
derived  from  a  single  animal,  are  there  preserved  (Nos.  159  and  160, 
Pathological  Series). 

In  the  teratological  series  of  the  same  museum  (No.  373)  is  a  pre- 
paration showing  a  lock  of  wool,  growing  from  a  dermoid  patch  on  the 
ocular  conjunctiva. 

Here  also  may  be  mentioned  the  occurrence  of  aberrant  teeth  in  cysts 
and  fistulse  of  the  neck,  between  the  angle  of  jaw  and  external  auditory 
meatus  ;  which  seem  to  arise  from  defective  closure  of  a  branchial  cleft, 
with  indications  of  a  tendency  to  the  formation  of  a  redundant  rudi- 
mentary mouth.  An  example  of  a  dentigerous  cyst  of  the  upper  jaw 
of  a  young  sheep,  associated  with  a  malformed  central  incisor,  may  be^ 
seen  in  St.  Bartholomew's  Hospital  Museum  (1  :  119a). 

Among  the  pseudo-plasms  of  sheep,  reference  must  be  made  to  coccidial 
tumours,  such  as  those  described  by  Nocard2  in  the  intestine. 

Tubercle  occurs  in  sheep,  and  even  in  goats  ;  and  not  so  very  rarely. 

Goat. 

Eggeling3  has  reported  a  case  of  mammary  cancer  in  a  female  goat 
(Capra  hircus). 

A  curious  form  of  quasi-malignant  tumour  of  the  anus  of  female 
Angora  goats  imported  from  South  Africa,  has  been  described  by  De 
Korte  ;4  which  strikingly  illustrates  the  difficulty  of  discriminating  certain 
tumours  in  animals  from  mycotic  pseudo-plasms  ;  for,  while  the  author 
regards  this  malady  as  a  true  malignant  tumour,  other  pathologists 
describe  it  as  a  granuloma. 

Goats   are   certainly   very   rarely   attacked   by   malignant   disease  ;X 
indeed,  the  above  are  the  only  modern  examples  of  the  kind  known  to 
me.    Large  odontoniata,  in  connexion  with  the  jaws,  have  been  met  with  ; 
and  these  have  sometimes  been  described  as  sarcomatous.     Cutaneous 
horns,  and  hydatid  cysts,  also  occur  in  goats. 

Deer. 

V  Deer  seem  to  be  as  little  liable  to  malignant  tumours  as  goats.  Otto 
refers  to  melanosis  in  a  stag,  but  I  cannot  cite  a  single  modern  instance. 
In  the  museums,  one  finds  specimens  of  fibroma  of  the  antler,  piliferous 

1  "Catalogue  of  Hunterian  Museum,  Glasgow,"  1900,  p.  393. 

2  Journal  of  Pathology,  etc.,  1893,  vol.  i.,  p.  404. 

3  Cited  by  Sticker,  Arch.  f.  klin.  Chir.,  1902,  Bd.  Ixv.,  p.  661. 
*  Transactions  of  the  Pathological  Society,  London,  1905. 


108  THE  NATURAL  HISTORY  OF  CANCER 

dennoid  of  the  conjunctiva,  exostosis  of  the  skull,  ossiform  tumour  from 
the  brain,  bony  deposits  in  the  omentum,  hydatid  cysts  etc. 


Rabbit. 

Malignant  tumours  are  certainly  of  extremely  rare  occurrence  in  these 
animals  ;  indeed,  hardly  any  really  reliable  case  records  exist.  Per 
contra ,  rabbits  are  so  exceedingly  subject  to  psorospermosis,  with  its 
attendant  tumour-like  lesions,  that — in  tame  animals — this  malady  may 
be  said  to  be  universal. 

A  few  years  ago  Lack *  claimed  to  have  succeeded  in  experimentally 
producing  cancer  in  a  rabbit,  the  uterus  being  one  of  the  structures 
implicated. 

Lack's  experiment  has  since  been  repeated  by  many  pathologists,  but 
no  one  has  succeeded  in  reproducing  similar  morbid  appearances. 

Shattock,2  having  had  occasion  to  examine  the  body  of  a  rabbit  that 
had  been  killed  as  obviously  diseased,  found  a  curious  tumour-like,  cystic, 
villous  new  formation,  having  the  general  aspect  of  a  "  chorionic  mole," 
invading  both  uteri.  Histological  examination  revealed  the  structure  of 
papilliferous  columnar-celled  epithelioma.  Similar  formations  were  found 
in  the  peritoneum.  The  author  regards  this  tumour  as  an  example  of 
spontaneous  uterine  cancer  ;  and  suggests  that,  in  Lack's  case,  the  disease 
probably  had  similar  origin. 

In  the  absence  of  special  examination  directed  to  the  exclusion  of 
psorosperms,  it  seems  undesirable  to  accept  these  cases,  as  being  scien- 
tifically verified  examples  of  uterine  cancer  in  the  rabbit ;  and  further 
observations  are  needed  to  establish  the  occurrence  of  this  condition  in 
these  animals. 

The  Museum  of  the  Royal  College  of  Surgeons  of  Ireland  contains  a 
specimen3  of  "  fungus  hsematodes  "  of  the  dorsal  surface  of  the  scapula 
of  a  rabbit — a  firm,  elastic,  nodular  tumour,  larger  than  a  goose's  egg, 
being  displayed. 

Rabbits  are  also  liable  to  melanosis.  Lubarsch4  has  lately  described 
a  large  renal  tumour  in  a  rabbit. 


Mouse. 

Until  the  many  various  parasitic  pseudo-plasms,  to  which  mice  and 
rats  are  specially  prone,  have  been  more  thoroughly  studied  and  dis- 
criminated, it  will  be  impossible  to  form  a  reliable  conclusion  as  to 
the  incidence  of  true  tumours  in  these  animals. 

Independently  of  the  so-called  "  Jensen's  tumour  "  and  its  variants, 
the  nature  of  which  will  be  discussed  in  a  subsequent  chapter,5  several 
instances  of  malignant  tumours  in  mice  have  been  reported. 

*  Journal  of  Pathology,  1900,  vol.  vi.,  p.  154. 

-  Transactions  of  the  Pathological  Society,  London,  1900,  vol.  li.,  p.  56. 

4  Cent.  SI. '/.  attg.  Path.,  etc.,  1903,  vol.  xvi.,  p.  9. 
6  Chapter  VTII. 


CANCER  AND  OTHER  TUMOURS  IN  ANIMALS          109 

Even  as  far  back  as  half  a  century,  Crisp  *•  exhibited  at  the  London 
Pathological  Society  a  malignant  tumour  of  the  pectoral  muscle  of  a 
wild  mouse,  caught  in  a  trap. 

According  to  the  Cancer  Research  pathologists,  11  cases  of  malignant 
disease  were  met  with  in  27,000  mice  examined ;  and  they  seem  to  be  of 
more  frequent  occurrence  in  tame  than  in  wild  varieties. 

Tumours  of  this  kind  have  been  met  with  in  the  mammary  region, 
skin,  jaw,  intestine,  lung,  vulva  etc.  Mice  are  also  subject  to  melanosis. 
Haaland  has  described  chondro-sarcoma  ;  and  Ehrlich  chondroma. 

Tyzzer2  has  reported  instances  of  two  independent  growths  in  the\7 
same  mouse — e.g.,  cylindrical  epithelioma  of  the  lung,  concomitant  with 
adenoma  of  the  kidney  etc.,  and  other  examples  of  so-called  "  sponta- 
neous "  tumours. 

With  regard  to  the  non-malignant  tumours  of  mice,  the  published 
records  known  to  me  are  exceedingly  scanty :  Spencer3  has  described 
an  instance  of  "  hornifying  excrescence  "  of  the  head  of  a  wild  mouse ; 
Treves4  a  similar  formation  on  the  neck ;  and  other  examples  of  this  kind 
may  be  found  in  the  museums.  Various  forms  of  adenoma  and  cyst- 
adenoma  have  also  been  reported. 

Quasi-malignant  growths  due  to  parasitic  sporozoa,  blastomycetes, 
bacteria,  pseudo- tuberculosis,  nematodes  etc.,  often  occur  ;6  and  some- 
times these  pseudo-plasms  also  mimic  non-malignant  tumours. 

According  to  Lydia  Rabinowitsch,  mice  and  rats  are  prone  to  tubercle, 
infected  animals  readily  conveying  the  disease  to  others  of  their  species. 


Rat. 

As  might  be  expected  a  priori,  there  is  great  similarity  with  regard 
to  neoplastic  proclivity,  between  rats  and  mice. 

Malignant  epithelial  and  connective-tissue  tumours,  do  undoubtedly 
occur  in  rats,  but  they  are  very  rare. 

A  good  example  of  ossifying  sarcoma  of  the  leg  bones  of  a  rat,  has 
been  described  and  figured  by  Bland-Sutton  ;5  and  these  animals  are  also 
liable  to  melanosis. 

The  epidemic  occurrence  of  so-called  "  cancer  "  in  rats,  as  well  as  a 
contagious  form  of  the  malady  transmissible  from  one  animal  to  another 
by  implantation,  as  in  the  case  of  mice,  have  also  been  reported  by 
several  pathologists — e.g.,  Hanau,  Eiselsberg,  Loeb,  Velich,  etc.  The 
claim  of  these  pseudo-plasms  to  be  regarded  as  true  malignant  tumours 
has  yet  to  be  substantiated  ;  all  the  indications  at  present  available 
seem  to  me  to  point  rather  to  their  affinity  with  the  granulomata  and 
"  infective  epithelioses,"  to  which  rats  are  as  prone  as  mice. 

Here  mention  may  be  made  of  the  fact  that  tumours  of  this  kind 

1  Transactions  of  the  Pathological  Society,  London,  1854,  p.  348. 

2  Journal  of  the  American  Medical  Association,  October  20,  1906,  p.  1237  ;  Fourth 
Rep.  Croft  Cancer  Commission,  Boston,  U.S.,  1907,  p'  27. 

3  Transactions  of  the  Pathological  Society,  London,  1890,  vol.  xli.,  p.  402. 

4  Transactions  of  the  Pathological  Society,  London,  1888,  vol.  xxxix.,  p.  463. 

5  Journal  of  Anatomy,  vol.  xix.,  p.  456. 

6  For  instances  experimentally  produced,  vide  Chapter  X. 


110  THE  NATURAL  HISTORY  OF  CANCER 

have  been  produced  in  rats,  by  inoculating  them  with  certain  pathogenic 
yeasts  (Busse,  Curtis,  Sanfelice,  Wlaeff  etc.). 

Non-malignant  tumours  seem  to  be  almost  as  uncommon  in  rats  as 
in  mice.  An  example  of  subcutaneous  fibroma  of  large  size,  has  lately 
been  reported  by  Lecene  and  Esmonet  ;l  and  in  a  pied  rat,  Bland-Sutton2 
met  with  a  similar  tumour  in  the  neck  ;  Shattock  3  has  described  adeno- 
fibroma  of  the  mamma  of  a  male  pied  rat ;  Loeb  4  adenoma  of  the  mamma 
of  a  female  rat ;  and  Bland-Sutton  ovarian  hydrocele. 

Other  Mammalian  Animals. 

An  interesting  instance  of  columnar-celled  epithelioma  of  the  ileum 
in  a  lion  has  been  described  by  Harrison  : 5  this  animal  was  born  in  the 
Clifton  Zoo,  and  passed  the  sixteen  and  a  half  years  of  his  life  in  a  com- 
paratively small  cage  there,  his  general  health  having  been  good.  He 
died  after  a  lingering  illness,  marked  by  progressive  wasting.  Post- 
mortem examination  revealed  a  circular  cancerous  growth,  constricting 
the  lumen  of  the  bowel,  just  above  the  ileo-csecal  valve,  which  on  micro- 
scopical examination  had  the  structure  above  mentioned. 

An  example  of  cancer,  in  an  aged  lioness,  has  been  reported  by  Welsh, 
of  Sydney,  New  South  Wales,  who  has  also  met  with  an  instance  of  the 
same  disease  in  an  old  tigress. 

Cystic  tumours  of  the  liver,  and  exostoses  of  the  vertebrae  and  other 
bones,  have  also  been  noted  in  lions ;  as  well  as  rounded  bodies,  like 
detached  fibromyoma,  loose  in  the  peritoneal  cavity. 

In  the  Glasgow  Hunterian  Museum,6  is  a  portion  of  a  leopard's  stomach, 
with  a  necrotic  fibroid  tumour  projecting  beneath  the  mucosa  ;  and 
Bland-Sutton  has  met  with  cystic  disease  of  the  ovaries  in  a  tigress. 

Many  years  ago,  E.  Rousseau  reported  that  malignant  tumours  were 
"'  not  infrequent,"  among  the  white  bears  confined  in  the  Jardin  des 
Plantes  at  Paris. 

An  instance  of  cancer  of  the  stomach  of  a  rhinoceros  has  lately  been 
cited  by  Renshaw. 

A  large  spongy  exostosis,  invading  the  superior  maxilla  and  adjacent 
bones  of  the  skull  of  a  hippopotamus,  has  been  seen  by  Otto  ;  and,  by  the 
same  pathologist,  odontoma  of  the  elephant's  tusk. 

Thick-walled  cysts  of  the  liver  of  the  porpoise  and  camel,  sometimes 
calcified,  are  preserved  in  museums. 

A  cancellous  bony  outgrowth  from  the  inferior  maxilla  of  the  Vir- 
ginian opossum  is  in  the  Hunterian  Museum  ;  which  also  comprises  two 
subcutaneous  dermoid  cysts,  with  steatomatous  laminated  contents,  one 
from  the  back  and  the  other  from  the  abdominal  region  of  the  same 
animal. 

Multiple  myomata  of  the  uterus  of  a  kind  of  beaver  (Myopotamus 
coypus),  have  been  described  by  Hilgendorf  and  Paulicki. 

1  Bull,  et  mem.  Soc.  Anat.,  Paris,  1905,  vol.  Ixxx.,  p.  38. 

2  Op.  cit. 

3  Transactions  of  the  Pathological  Society,  London,  1893,  vol.  xliv.,  p.  229. 
*  Journal  of  Medical  Research,  1902,  vol.  viii.,  p.  46. 

5  Op.  cit. 

6  Anatomical  and  pathological  collection  (34  :  15). 


CANCER  AND  OTHER  TUMOURS  IN  ANIMALS  111 

Whales  are  subject  to  warty  outgrowths  of  the  skin,  which  are  often 
due  to  parasitic  cirripedia  ;  as  described  by  Weltner. 

A  malignant  renal  tumour  (derived  from  an  adrenal  "  rest  "),  has 
been  described  by  Bland-Sutton  in  a  marmot  ;  the  same  author  has  also 
met  with  odontoma  in  this  kind  of  animal ;  and  Otto  has  seen  "  spina 
ventosa  "  of  the  inferior  maxilla. 

Even  in  marsupial  animals,  a  feAv  instances  of  malignant  and  other 
tumours,  have  been  reported. 

In  the  Hunterian  Museum  (No.  1,038,  Pathological  Series)  in  one  half 
of  the  inferior  maxilla  of  a  kangaroo,  distended  by  a  large  central  ossifying 
sarcoma  ;  and,  according  to  Otto,  specimens  of  "  spina  ventosa  "  and 
exostoses,  in  marsupial  animals,  may  often  be  seen  in  museums. 

Examples  of  in tr a- abdominal  lympho-sarcoma  in  dasyures,  have  been 
described  by  Eve  and  Bland-Sutton  ;  while,  the  latter  author,  has  also  seen 
cancer  of  the  marsupial  pouch  of  a  short-headed  phalanger. 


Birds. 

It  is  stated  by  Pick  and  Poll,  that  malignant  tumours  are  of  very 
rare  occurrence  in  birds ;  but,  if  this  is  meant  to  apply  to  the  common 
domesticated  kinds,  it  cannot  be  accepted  as  quite  accurate  ;  for,  as 
Heusinger  long  ago  pointed  out,  malignant  tumours  are  not  so  very 
uncommon  in  these,  and  this  is  quite  in  accord  with  modern  indications. 

The  common  domestic  hen  seems  to  be  remarkably  prone  to  sarcoma, 
instances  having  been  reported  by  Hathaway,  Patterson,  Birchmore, 
Crisp,  Parker  etc. ;  melanosis  also  occurs.  Squamous-celled  epithelioma 
of  the  floor  of  the  mouth  has  been  described  by  Pick  ;  an  enormous  quasi- 
malignant  ovarian  tumour  by  Bland-Sutton ;  and  two  instances  of 
epithelioma  of  the  small  intestine  by  Ehrenreich  and  Michaelis. 

A  large  fibre-cartilaginous  tumour,  from  the  subcutaneous  tissue  of 
the  thigh  of  a  domestic  fowl,  is  to  be  found  in  the  Museum  of  the  Royal 
College  of  Surgeons  of  Ireland  ;  and  a  large  fatty  tumour  was  removed  from 
the  pectoral  region  of  a  hen  by  Crisp.  Ehrenreich  and  Michaelis  have 
described  two  examples  of  fibroma  of  the  mesentery.  Exostoses,  hyper- 
ostoses,  and  ossified  tendons,  are  not  particularly  rare  ;  while  sebaceous 
cysts,  hornifying  outgrowths,  warts,  and  even  corns,  are  fairly  common. 

Large  cystomata  of  the  hen's  ovary  are  often  met  with,  as  the 
specimens  in  many  museums  testify. 

Mougie  has  seen  a  large  serous  cyst  of  the  abdomen  of  a  hen  ;  and 
dermoid  cysts,  containing  feathers,  also  occur. 

A  quasi-sarcomatous  tumour  from  the  lung  of  a  Bernicle  goose  is 
preserved  in  Guy's  Hospital  Museum  (No.  1,793,  Pathological  Series).  In 
the  Museum  of  the  Irish  College  of  Surgeons  (D.  f.,  56),  is  an  immense 
"  fibroid  "  tumour,  "  as  big  as  a  large  melon,"  which  occupied  nearly  all 
of  the  greatly  distended  abdominal  cavity  of  a  goose  ;  this  tumour  was 
so  slightly  attached  that,  when  the  abdomen  was  opened,  it  fell  out,  so 
that  its  exact  point  of  attachment  could  not  be  determined,  but  it  was 
surmised  to  have  originated  from  the  oviduct  or  intestine.  Harrison  1 
1  Bristol  Med.-Chir.  Journ.,  1894,  vol.  xii.,  p.  288. 


112  THE  NATURAL  HISTORY  OF  CANCER 

met  with  a  similar  tumour,  which  weighed  at  least  one  pound,  in  an  ancient 
goose  supposed  to  be  over  thirty  years  old,  which  died  in  the  Clifton 
Zoo ;  and  in  this  instance  the  pedicle  of  the  tumour  was  connected  with 
the  mesentery.  A  large,  lobulated,  quasi-fibrous  tumour,  from  the  neck 
of  a  goose,  is  in  the  Hunterian  Museum  (No.  307,  Pathological  Series). 
Dermoid  cysts,  containing  feathers,  have  also  been  found  in  these  birds. 

Other  examples  of  tumours  in  birds  of  which  I  have  cognizance  are  : — 
A  subcutaneous  round-celled  sarcoma,  of  yellow  colour,  of  the  wing  of  a 
dove  (Woods  Hutchinson)  ;  alveolar  sarcoma  of  the  pectoral  region  of  a 
golden  plover,  in  the  Hunterian  Museum  ;  malignant  tumour  of  the 
pectoral  region  of  a  canary  (Crisp)  ;  "  fungoid  "  tumour  of  the  eye  of  a 
canary  (Crisp);  "  spina  ventosa"  of  the  great  wing-bone  of  a  parrot, 
cited  by  Otto  ;  myxo-sarcoma  of  the  pectoral  muscles  of  an  Indian 
parakeet  (Bashford)  ;  malignant  tumours  among  the  carnivorous  birds 
of  the  Paris  Jardin  des  Plantes,  noted  by  Rousseau  ;  ovarian  tumour  in  a 
pheasant,  by  Slater  ;  large  sebaceous  cyst  of  the  pectoral  region  of  a 
pigeon,  in  the  Irish  College  of  Surgeons'  Museum  ;  I  had  a  thrush  which 
developed  a  similar  cyst  on  the  head,  whence  sprang  a  horn-like  out- 
growth ;  and  formations  of  this  kind  have  been  seen  in  other  birds  (dove, 
canary,  partridge)  ;  fibroma  of  the  thigh  of  a  grouse  in  the  Hunterian 
Museum  ;  the  oldest  inhabitant  of  the  Clifton  Zoo,  a  griffin  vulture,  was 
subject  to  an  exostosis  of  the  foot,  as  reported  by  Harrison  ;  turkeys  seem 
to  have  special  proclivity  to  large  ivory  exostoses  of  the  bones,  of  which 
there  are  specimens  in  the  Hunterian  and  other  museums,  to  which 
J.  Hutchinson  *  has  specially  called  attention ;  on  each  metatarsal  bone 
of  a  young  rhea  Bland-Sutton  found  an  enchondromatous  tumour  ; 
among  the  Hunterian  preparations  in  the  English  College  of  Surgeons' 
Museum,  is  :  "A  tumour  from  the  belly  of  an  ostrich  "  of  fibre-cellular 
structure  ;  also  an  exostosis  on  a  cervical  vertebra  of  the  same  bird ;  and 
a  cyst  developed  from  an  unobliterated  vitello-intestinal  duct,  attached 
to  the  intestine  of  an  emu. 

Contagious  tumour-like  lesions  due  to  tubercle,  psorospermosis  and 
other  parasitic  infections  are  common  in  birds.  To  this  list  the  con- 
tagious inoculable  malady  called  Molluscum  contagiosum,  especially  prone 
to  occur  in  fowls  and  pigeons,  must  be  added  ;  and  its  similarity  with  the 
like-named  malady  of  human  pathology  is  also  noteworthy. 

Birds  are  as  a  class  very  prone  to  tubercle,  especially  the  common 
domesticated  kinds. 

Reptiles  and  Amphibians. 

With  regard  to  these  groups  of  animals  all  that  can  be  said  is,  that 
malignant  and  benign  tumours  are  known  to  occur  among  some  of  their 
members.  By  systematic  post-mortem  examination  of  the  bodies  of 
salamanders  from  the  Berlin  Biological  Institute,  Pick  and  Poll 2  have 
demonstrated  cystic  glandular  cancer  of  the  testis  of  the  giant  sala- 
mander (Crypto-branchus  japonicus).  These  pathologists  have  also  found 
a  benign  tumour,  which  they  regard  as  thyroid  adenoma,  growing  from 

1  Archives  of  Surgery,  1893,  vol.  iv.,  p.  121. 

2  Berlin,  klin.  Woch.,  1903,  No.  23,  S.  518  ;  No.  24,  S.  546  ;  and  No.  25,  S.  572. 


CANCER  AND  OTHER  TUMOURS  IN  ANIMALS  113 

the  neck  of  the  snake-necked  tortoise  ;  and  also  a  tumour,  as  to  the  nature 
of  which  they  are  doubtful,  growing  from  the  left  side  of  the  neck  of  a 
Salamandra  maculata.  Plehn1  has  collected  records  of  other  cases  of 
tumours  in  salamanders,  lizards,  and  frogs. 

A  specimen  of  columnar-celled  cancer  of  the  kidney  of  a  frog  (Small- 
woods),  has  been  verified  by  the  Cancer  Research  Staff. 

An  interesting  example  of  cancer  of  the  ovaries  with  widespread 
dissemination,  in  a  python,  that  had  lived  for  fifteen  years  in  the  London 
Zoo,  where  it  died  cachectic  on  account  of  this  ailment,  has  been  described 
by  Bland-Sutton ; 2  and  this  author  has  also  met  with  multiple  chondro- 
mata,  in  a  rachitic  Indian  lizard,  from  the  same  collection  of  animals. 

Sarcoma  in  a  frog  has  been  reported  by  Murray  ;  and  Gebhardt  has 
investigated  two  pyloric  tumours  in  frogs,  due  to  protozoa. 

Otto  has  seen  "  spina  ventosa  "  of  the  caudal  vertebrae  of  a  chameleon  ; 
and  there  is  a  specimen  showing  exostoses  on  the  ribs  of  a  chameleon,  in 
the  Hunterian  Museum  (No.  797). 

Sandifort  has  met  with  exostoses  on  two  vertebrae  of  a  boa-constrictor. 

Fish. 

We  have  to  note  the  great  proclivity  of  fishes  to  parasitic  infections 
of  various  kinds  (sporozoa,  mycoses,  bacteria,  nematodes  etc.),  many 
of  which  cause  large  swellings,  which  resemble  malignant  tumours.3 
Epidemics  among  river  fishes  (barbel,  pike  etc.),  due  to  parasitic  myxo- 
sporidia,  have  been  noted  in  Germany ;  and  this  form  of  disease  is  common 
in  the  pike's  bladder. 

From  a  crowd  of  parasitic  pseudo-plasms,  the  Cancer  Research  Staff 
claim  to  have  demonstrated  sixteen  examples  of  true  malignant  tumours 
in  fishes,  some  of  them  pelagic  ;  but,  long  before  this  body  took  the 
matter  up,  instances  of  malignant  tumours  in  fish  had  been  reported, 
especially  in  carp,  by  Crisp,  Bland-Sutton,  Sibley,  Ohlmacher,  and  others. 

Carp  have  been  kept,  under  artificial  conditions,  from  the  remotest 
times ;  and,  it  is  not  without  significance,  that  just  this  fish  should  have 
furnished  so  many  examples  of  malignant  tumours. 

A  sarcomatous  tumour  from  a  golden  carp,  has  been  described  and 
figured  by  Bland-Sutton,4  from  a  specimen  in  the  Hunterian  Museum  ;  a 
similar  tumour  of  much  larger  size,  also  in  a  carp,  had  previously  been 
described  by  Crisp  ; 5  examples  of  malignant  epithelial  tumours  in  carp 
have  been  reported  by  Battaillon,6  and  Bashford.7  Sibley,8  having 
examined  a  specimen  labelled  "  multiple  sarcoma  of  a  carp  "  from  a 
German  pathological  museum,  found  that  the  tumours  consisted  almost 
entirely  of  psorospermia. 

1  Zeitschr.  f.  Krebsforschung,  1907. 

2  Journal  of  Anatomy,  vol.  xix.,  p.  464. 

3  For  some  interesting  remarks  on  this  subject,  vide  Gurley  and  Tyzzer,  "  Tumours 
and    Sporozoa    in   Fishes,"   First  Annual  Report  of  the  Cancer  Committee,   Harvard 
Medical  School,  Boston,  U.S.,  October,  1900,  etc. 

*  Journal  of  Anatomy,  vol.  xix.,  p.  447. 

6  Transactions  of  the  Pathological  Society,  London,  vol.  v.,  p.  347. 

6  Zeite.  f.  Fleisch.  u.  Mikh.-Hyg.,  1898,  S.  151. 

7  Scientific  Reports  of  the  Cancer  Research  Fund,  1905,  No.  2. 

8  Transactions  of  the  Pathological  Society,  London,  1890,  vol.  xli.,  p.  322. 

8 


114  THE  NATURAL  HISTORY  OF  CANCER 

Lately,  several  instances  of  "  cancer  epidemics  "  in  trout,  have  been 
reported  by  Pick,  Scott,  Gilruth,  Bashford  etc. ;  and,  in  all  these  cases,  the 
fish  had  been  long  kept  under  artificial  conditions  in  special  "  hatcheries." 

Two  examples  of  malignant  tumours  from  fish  (cod,  gurnard),  which 
had  lived  under  natural  conditions,  have  also  been  studied  by  the  Cancer 
Research  Staff  i1  and  Ohlmacher  has  seen  sarcoma  of  the  peri- vertebral 
connective  tissue,  with  metastases,  in  a  lake  pike. 

Curious  tumours  due  to  sporozoa,  in  a  minnow  (Cyprinus  phoxinus), 
have  been  described  by  Davaine  ;  and,  in  a  stickleback  (Gasterosteus 
trachurus),  by  L.  Tait  ;  while,  in  the  Hunterian  Museum,  is  a  dace 
(Cyprinus  lenciscus),  the  surface  of  whose  body  is  covered  by  "  a 
mycoderm  confervoid  growth  "  (No.  2,305). 

A  striking  feature  in  the  neoplastic  pathology  of  fishes,  is  the  great 
frequency  of  exostoses  and  bony  tumours,  wrhich  are  generally  multiple. 

In  the  chief  pathological  museums,  many  specimens  illustrating  the 
proneness  of  codfish  to  multiple  exostoses  and  bony  tumours  are  to  be 
found ; 2  their  seats  of  election  are  the  vertebrae,  superior  maxilla,  tail 
etc.  In  the  stomach  of  these  fish,  submucosal  "  fibroid  "  has  been  met 
with  ;  and  a  similar  tumour  has  been  found  in  the  subcutaneous  connective 
tissue.  Specimens  of  the  sclerotic  of  the  eye  of  a  codfish,  exhibiting 
numerous  white  nodules,  due  to  parasitic  gregarinse,  are  preserved  in  the 
Glasgow  Hunterian  Museum  (39  :  32).  As  previously  mentioned,  spindle- 
celled  sarcoma  of  the  air-bladder  of  a  codfish,  has  been  investigated  by 
the  Cancer  Research  Staff  ;  also  intra-abdominal  glandular  cancer  in  a 
gurnard. 

Multiple  bony  tumours  of  the  skeleton  of  some  chaetodons  are  of  such 
common  occurrence  that  W.  Bell,  who  first  specially  called  attention  to 
them,  rather  rashly  concluded  that  they  were  "  natural  "  in  this  fish. 

Large  bony  tumours  of  the  occipital  region  of  the  skull  etc.  are  also 
often  met  with  in  Ephippus  gigas  and  faber,  as  reported  by  Valenciennes. 

Otto  long  ago  called  attention  to  the  frequency  of  large  exostoses, 
connected  with  the  spines  of  the  vertebrae  of  scabbard  fish  (Lepidopus 
peronii  etc.),  and  of  the  spiny  fish  (Sparus  erythrinus)  ;  Gervais  has  since 
confirmed  and  extended  these  observations,  describing  a  large  bony 
outgrowth  from  the  occipital  crest  of  Pagrus  unicolor. 

Exostosis  of  the  jaw-bone  of  a  pike  has  also  been  described. 

The  Anatomical  and  Pathological  Museum  of  the  College  of  Surgeons 
of  Edinburgh  (5  :  1726),  contains  a  specimen  showing  extreme  hyper- 
ostosis  of  many  caudal  vertebrae,  from  a  haddock  ;  and,  in  the  Glasgow 
Hunterian  Museum,  a  portion  of  one  of  these  fishes  is  exhibited,  so  as  to 
display  the  innumerable  colonies  of  psorospermia  parasitic  in  its  flesh 
(39  :  33). 

1  Scientific  Reports,  No.  1,  1904,  p.  7. 

2  Glasgow  Hunterian  Museum,  Nos.  5,  172,  and  172a  ;  and  in  the  London  Hunterian 
Museum,  Nos.  796  and  1,039. 


CHAPTER  VI 
TUMOURS  IN  VEGETABLE  ORGANISMS 

IN  this  chapter  I  propose  to  show:  (1)  that  tumours,  analogous  to  the 
malignant  and  non-malignant  tumours  of  human  and  animal  pathology, 
occur  also  in  vegetable  organisms  ;  (2)  that  such  tumours  are  dervied  from 
abnormally  evolving  buds  ;  and  (3)  that  in  the  vegetable  world  tumour- 
like  formations  are  of  very  common  occurrence,  as  the  consequence  of 
parasitic  and  other  irritants  ab  extra. 

Bud  Formation  and  its  Anomalies. 

The  process  of  gemmation  in  plants  is  of  great  importance,  for  the 
understanding  of  their  development  and  organization  ;  and  it  is  capable 
of  throwing  much  light  on  the  analogous  processes  in  animal  and  human 
ontogeny,  to  which  biologists  and  pathologists  have  hitherto  paid  far  too 
little  attention — for  gemmation  has  its  pathological  as  well  as  its  physio- 
logical outlets.  The  simplest  buds  consist  either  of  single  undiffer- 
entiated  cells,  or  of  groups  of  such  cells  derived  from  single  cells,  the 
differentiated  tissues  of  the  parent  plant  having  no  share  in  the  formation 
of  the  primitive  bud,  and  no  connexion  with  it  until  a  later  period. 

Usually  buds  develop  in  organic  connexion  with  the  parent  stock  ; 
but  sometimes,  as  in  the  tiger-lily,  they  fall  off  and  develop  separately 
(bulbils).  The  branch-bud  here  acts  like  a  seed-bud,  but  is  capable  of 
developing  without  fertilization.  Hence  buds  artificially  separated,  may 
be  used  for  purposes  of  propagation,  as  in  the  familiar  processes  of 
grafting,  budding,  layering,  etc.  Thus,  each  bud  is  potentially  a  new 
individual  having,  under  favourable  circumstances,  the  power  of  evolving 
into  a  perfect  organism. 

But  the  degree  of  development  actually  attained,  usually  falls  far  short 
of  this  ;  for,  owing  to  disturbances  in  nutrition,  buds  may  be  variously 
modified  in  adaptation  to  other  ends.  Thus,  in  extreme  cases,  they  may 
remain  permanently  undeveloped  ;  or  they  may  remain  for  long  periods, 
even  for  years,  in  a  dormant  or  latent  state  ;  and  yet,  under  favourable 
conditions,  their  activity  may  revive. 

When  their  development  is  somewhat  less  restricted,  the  products  may 
be  dwarfed,  or  evolved  into  spines,  tendrils,  twigs,  or  various  irregular 
formations,  which  may  properly  be  called  tumours. 

In  the  higher  vegetable  organisms  buds  are  usually  distributed  with 
great  regularity,  being  either  terminal  or  axillary  ;  buds  arising  in  any 
other  way,  are  said  to  be  of  adventitious  origin. 

115  8—2 


116  THE  NATURAL  HISTORY  OF  CANCER 

Now,  adventitious  buds  differ  from  normal  buds  only  in  respect  to 
position  ;  for,  they  originate  otherwise  in  precisely  the  same  way,  as  those 
normally  formed  on  the  axis.  Adventitious  buds  have  been  found  on 
almost  every  part  of  plants.  They  sometimes  develop  in  extraordinary 
numbers  on  the  stems  and  branches  of  trees,  owing  to  some  interference 
with  the  vegetation  of  the  normal  buds  ;  and  they  may  be  evoked  by 
wounds.  When  a  begonia  leaf  is  placed  in  damp  soil,  and  incisions  are 
made  across  its  "  nerves,"  buds  spring  from  every  incision ;  and  as  many 
fresh  plants  may  be  obtained  in  this  way  as  the  leaf  has  received  wounds. 
The  Dutch  bulb  growers  have  cleverly  availed  themselves  of  a  similar 
property,  to  propagate  hyacinths  ;  this  they  effect  either  by  making  two 
or  three  deep  incisions  into  the  base  of  the  bulb — destroying  the  nascent 
flower-stalk — when,  after  a  short  time,  numerous  small  buds  form  along 
the  edges  of  the  cut  surface  ;  or,  by  scooping  out  the  interior  of  the  base 
of  the  bulb,  and  so  leaving  exposed  the  cut  ends  of  the  sheathing  leaves, 
from  which  buds  soon  spring  in  great  numbers. 

Leaves  subjected  to  slight  pressure,  and  in  process  of  decay,  frequently 
develop  buds  in  a  similar  way. 

Degrees  of  injury  which  fall  far  short  of  this,  such  as  those  produced 
by  various  mild  irritants,  as  described  by  Waldenburg,  cause  local 
thickenings,  owing  to  increased  growth  and  proliferation  of  the  cells  of 
the  part. 

In  like  manner,  as  will  be  seen  in  the  sequel,  the  various  kinds  of  galls 
arise. 

In  a  general  way,  the  root  is  distinguished  from  the  stem  by  the 
absence  of  buds  ;  but,  under  exceptional  circumstances,  adventitious  buds 
may  form  even  on  roots.  Duhamel,  having  planted  a  willow  with  its 
branches  in  the  ground  and  its  roots  in  the  air,  saw  its  roots  become 
covered  with  leaf-bearing  buds,  while  the  buried  branches  produced  roots. 
The  production  of  a  flower-bud  has  been  noticed  on  the  root  of  a  species 
of  Impatiens.  In  some  cases,  the  divided  root  suffices  for  the  reproduction 
of  the  entire  plant,  as  in  the  Japan  quince,  the  Osage  orange,  and 
especially  the  Paulownia — the  roots  of  which,  even  when  cut  into  small 
pieces,  can  develop  into  perfect  trees. 

There  are  many  plants  which  produce  buds  on  their  leaves.  This  is 
of  much  commoner  occurrence  among  the  lower  orders,  and  the  ferns, 
than  with  the  Phanerogamia.  As  examples  among  native  plants  may  be 
instanced  the  watercress,  Cardamine  pratensis,  and  Malaxis  paludosa — 
in  the  last  named,  the  buds  are  known  to  be  derived  from  single  cells  of 
the  surface  of  the  leaves.  Begonias  exhibit  this  power  in  a  remarkable 
degree  ;  in  some  instances,  single  scales  from  the  leaves  or  stem  habitually 
develop  into  young  plants.  One  of  the  best-known  instances  is  that 
afforded  by  Bryophyllum  calycinum,  a  succulent  tropical  plant,  whose 
leaves  produce  buds  furnished  with  roots,  stem,  and  leaves,  at  the  ex- 
tremities of  its  lateral  nerves.  These  buds,  which  fall  off  spontaneously 
and  root  in  the  earth,  may  be  compared  to  ovules  which  do  not  need  to 
be  fertilized  before  developing  ;  and  the  leaf  of  the  Bryophyllum  may  be 
regarded  as  an  open  carpel,  in  which  the  seeds  have  been  developed  by 
nutritive  action  alone.  Consideration  of  the  subject  in  this  light,  leads  us 


TUMOURS  IN  VEGETABLE  ORGANISMS 


117 


to  regard  the  bud  as  an  individual  vital  centre  resembling  the  ovule. 
Many  facts  in  vegetable  physiology  and  pathology  confirm  this  view. 
Schleiden  regarded  the  ovule  as  a  modified  bud,  and  the  now  well-authenti- 
cated cases  of  parthenogenesis  in  plants  support  his  theory.  In  these 
cases,  new  individuals  are  developed  from  unimpregnated  ovules,  as  from 
buds,  the  defect  in  the  ovular  reproductive  power,  which  ordinarily 
renders  impregnation  necessary,  being  removed.  The  ovule  or  seed-bud, 
then,  differs  from  the  branch-bud  essentially  only  in  this  :  that  it  generally 
needs  for  its  development  the  fertilizing  influence  of  the  pollen.  The 
fecundity  of  Bryophyllum,  completes  the  analogy  between  the  bud  and  the 
fertilized  ovule.  According  to  Hofmeister,  the  buds  of  Bryophyllum 
arise  before  the  complete  unfolding  of  the  leaf,  as  small  masses  of  un- 
differentiated  parenchyma,  in  the  deepest  parts  of  the  crenations  of  the 
leaves. 

Buds  thus  arising,  may  take  root  and  give  origin  to  leaf-bearing 
branches,  while  still  in  connexion  with  the  parent  plant,  as  in  Drosera 


FIG.  1. — AN  ADVENTITIOUS  LEAF-BEARING  SHOOT  DEVELOPED  ON  A  LEAF  OF 
EPISCIA  BICOLOR  (MASTERS). 

intermedia,  Episcia  bicolor  etc.  (Fig.  1),  though  they  generally  develop 
more  readily  after  the  leaves  have  fallen  off.  Adventitious  buds  have  also 
been  found  on  the  petiole,  lamina,  stipule  ;  and,  in  short,  on  every  part  of 
the  leaf.  It  thus  seems  as  if  buds  may  arise  wherever  undifferentiated 
cells,  still  capable  of  growth  and  development,  are  present. 

Such  facts  as  the  foregoing  show,  that  there  is  no  specific  distinction 
between  somatic  and  germ  cells,  as  Weismann  has  maintained  ;  they 
indicate  that  the  reproductive  properties  manifested  by  somatic  and  germ 
cells  are  the  same  in  kind,  and  that  they  differ  only  in  degree.  In  short, 
the  whole  history  of  gemmation  in  plants,  testifies  against  fundamental 
difference  between  somatic  and  germ  cells. 

It  seems  probable  that  the  capacity  of  the  higher  vegetable  organisms, 
for  manifesting  these  anom'alous  kinds  of  bud  formation,  may  be  due  to 
reversion  ;  at  any  rate,  they  remind  us  of  the  proliferous  outgrowths  so 
common  among  the  Thallophyta. 

The  shoots  which  spring  from  buds  usually  develop  into  structures 
of  the  same  form,  as  those  which  compose  the  parent  plant ;  but,  it  occasion- 


118 


THE  NATURAL  HISTORY  OF  CANCER 


ally  happens,  that  particular  buds  develop  differently  from  others  of  the 
same  stock. '  Gardeners  call  these  changes  "  sports  "  ;  by  Darwin  they 
were  described  as  ';  bud  variation  "  ;  while  De  Vries  discriminates  all 
abrupt  transformations  of  this  kind  as  "  mutations."  The  common 
moss-rose  is  considered  by  Darwin  to  have  originated  in  this  way  from  the 
Provence  rose. 

Not  only  normal,  but  adventitious  buds  as  well,  are  liable  to  this  kind 
of  mutation.  Fronds  of  the  same  fern,  for  instance,  often  manifest 
striking  morphological  variations  ;  of  this  a  remaikable  example  is  figured 
below  (Fig.  2),  which  represents  a  portion  of  a  frond  of  Pteris  quadriaurita 
bearing  an  adventitous  bud,  whence  foliage — very  different  from  that 
of  the  rest  of  the  plant — has  emerged.  Mutations  of  this  kind,  are  of 


FIG.  2.— PORTION  OF  A  FROND  OF  PTERIS  QUADRIACRITA,  IN  WHICH  THE  FOLIAGE 
EMERGING  FROM  AN  ADVENTITIOUS  BUD  IS  VERY  DIFFERENT  FROM  THAT  OF  THE 
BEST  OF  THE  PLANT  (MASTERS).  , 

much  commoner  occurrence  among  the  lower  than  among  the  higher 
orders  of  plants  ;  and  among  cultivated  than  among  wild  species. 

Many  mutations  were  regarded  by  Darwin  as  due  to  reversion  ;  others 
he  ascribed  to  the  so-called  "  spontaneous  variability,"  understanding 
by  this  term  variation  of  which  the  causes  were  not  obvious.1 

In  formulating  the  doctrine  of  natural  selection,  which  is  peculiarly 
his  own,  there  can  be  no  doubt  that  Darwin  failed  to  attach  due  weight 
to  the  occurrence  of  mutations  independently  of  selection  and  of  adapta- 
tion. It  has  since  been  shown  that  numerous  variations  of  this  kind  do 
occur,  some  of  which  are  obviously  disadvantageous  to  their  modified 
possessors,  while  others  are  neither  advantageous  nor  disadvantageous. 

It  is  with  these  mutations  that  the  various  pathological  new  formations 
should  be  classed.  Here  brief  reference  must  be  made  to  the  conditions 

1  According  to  H.  Spencer  :  "  Spontaneous  variations  are  interpretable  as  results  of 
miscellaneously  compounding  the  changes  wrought  in  different  lines  of  ancestors  by 
different  conditions  of  existence." 


TUMOURS  IN  VEGETABLE  ORGANISMS  119 

which  determine  the  incidence  of  gemmation,  gamogenesis,  and  alterna- 
tion of  generations  ;  and,  it  will  suffice  for  our  immediate  purpose,  if  I  state 
that  the  conclusion  derived  from  the  consideration  of  the  ensemble  of 
this  important  subject  is,  that  the  outcome  of  growth  in  any  particular 
case  is  mainly  determined  by  nutrition.  Thus  gemmation  or  asexual 
multiplication  may  be  regarded  as  the  outcome  of  favourable  nutritive 
conditions,  resulting  in  vegetative  growth  ;  while  gamogenesis  is  likely  to 
ensue  when  these  conditions  are  less  favourable.  From  this  standpoint, 
gemmation  and  tumour  formation  in  the  higher  organisms,  are  instances 
of  reversion  from  dominant  gamogenesis  to  the  asexual  process  ;  and 
the  genesis  of  malignant  and  other  tumours  is  a  phenomenon  of  the  same 
order  as  discontinuous  growth  in  general. 

Thus  the  origin  of  buds,  as  well  as  their  subsequent  development,  is 
chiefly  determined  by  the  conditions  of  nutrition.  Wherever  there  is  an 
excess  of  nutritive  materials,  capable  of  being  utilized  for  growth  by  the 
cells  of  the  part,  there  buds  may  arise. 


Vegetable  Tumours  and  Gemmation. 

From  the  consideration  of  these  interesting  processes,  we  must  now 
pass  to  the  closely  allied  subject  of  vegetable  tumours  ;  which,  as  I  shall 
proceed  to  show,  are  the  outcome  of  abnormal  bud  evolution. 

We  shall  find  that  in  these  cases,  the  local  changes  are  modelled  after 
the  processes  of  normal  growth,  and  that  both  are  subject  to  tne  same 
laws.  Changes  of  nutrition,  causing  altered  growth  and  impaired 
development,  seem  to  be  the  common  aetiological  factors  underlying  all  of 
these  abnormal  formations. 

Their  physiological  prototypes  must  be  sought  in  such  kindred 
processes,  as  those  above  described.  The  clear  recognition  of  this  import- 
ant truth  is  likely  to  lead  to  great  results,  in  the  future  development  of 
this  branch  of  pathology. 

I  think  there  can  be  no  doubt  that  the  neoplastic  process  can  be  more 
satisfactorily  studied  in  plants  than  in  animals,  owing  to  the  absence, 
in  the  former,  of  many  factors — such  as  nerves  and  bloodvessels — which, 
in  the  latter,  complicate  and  obscure  the  essential  nature  of  the  process. 
In  plants,  the  early  animal  embryo,  and  in  the  lower  animals,  all  the  phem> 
niena  of  growth  go  on  without  either  nerves  or  bloodvessels.  And  so  it 
is,  at  the  outset,  with  all  morphological  variations,  including  bud,  cancer, 
and  tumour  formations.  In  all  these  cases  the  nerves  and  bloodvessels 
have  not  the  slightest  direct  influence. 

By  bearing  in  mind  these  simple  but  fundamentally  important  con- 
siderations, we  are  at  once  able  to  get  rid  of  that  incubus  of  nineteenth- 
century  tumour  pathology — the  Broussaisian  doctrine — which  regards 
tumour  formation  as  an  outcome  of  ''  inflammation,"  rather  than  as  an 
anomaly  of  growth  ;  for,  in  the  vegetable  world,  as  in  the  lowly  organized 
part  of  the  animal  kingdom,  "  inflammation,"  in  the  proper  sense  of  the 
term,  is  impossible,  owing  to  the  absence  in  these  organisms  of  that  co- 
ordinated lymph- vascular  and  nervous  mechanism,  which  is  the  essential 


120  THE  NATURAL  HISTORY  OF  CANCER 

apparatus  by  which  alone  the  phenomena  of  "  inflammation  "  can  be 
produced,  as  I  shall  have  occasion  to  point  out  in  the  sequel. 

My  investigations  as  to  the  nature  of  tumours  in  trees  have  led  me  to 
classify  them  into  three  main  groups. 

The  first  group  comprises  those  circumscribed  woody  nodules  so  com- 
monly found  beneath  the  bark  of  the  beech,  elm,  oak,  cedar,  holly,  and 
other  trees,  to  which  the  vaguely  used  term  "  knaur  "  is  commonly 
applied. 

I  have  in  my  possession  a  typical  example,  on  a  small  scale,  from  an 
elm-tree.  An  ovoid  swelling,  about  the  size  of  a  Tangerine  orange, 
projects  beneath  the  bark  of  one  of  the  branches.  Its  surface  is  devoid 
of  buds  and  shoots.  On  section,  it  is  seen  to  be  composed  of  dense  wood, 
covered  with  rather  thickened  bark.  Examination  of  the  cut  surface 
shows  that  the  tumour  has  been  formed  round  two  centres  of  development, 
each  of  which  is  surrounded  by  its  own  system  of  concentric  woody 
laminae.  These  concentric  systems  are  embedded  in  other  woody  laminae, 
derived  from  the  investing  cambium  layer,  and  consequently  disposed 
parallel  with  the  axis  of  the  branch.  The  nodules  have  thus  been  partially 
embedded  in  the  woody  tissue  of  the  branch,  and  have  lost  their  direct 
connexion  with  the  cambium  layer.  A  narrow  ligneous  pedicle  connects 


FIG.  3.— SHOWING  FIVE  CIRCUMSCRIBED  TUMOURS  ra  THE  BARK  OF  A  HOLLY- TREE 

(NATURAL  SIZE). 

the  tumour  with  the  wood  of  the  branch.  At  the  free  extremity  of  the 
tumour,  it  is  interesting  to  observe  a  separate  woody  nodule,  the  size 
of  a  small  pea,  completely  isolated  in  the  cambium  layer.  This  may  be 
taken  as  illustrating  an  early  stage  in  the  development  of  such  growths, 
which  originate  from  disorderly  evolving  adventitious  buds. 

Mr.  S.  Paget  has  presented  some  good  examples  of  these  tumours  to 
the  Hunterian  Museum,  where  they  may  now  be  seen.  They  are  generally 
single,  but  occasionally  several  are  found  close  together,  as  was  the  case 
in  one  of  Paget's  specimens,  figured  above  (Fig.  3).  This  is  described  in 
the  catalogue  (No.  546A)  as  a  portion  of  the  bark  of  a  holly-tree,  with 
the  cambium  layer,  and  a  small  portion  of  the  wood.  Deep  in  the  sub- 
stance of  the  bark  are  five  rounded  tumours  composed  of  hard  wood, 
their  cut  surfaces  showing  faint  concentric  lamination.  At  the  upper  part 
of  the  specimen,  three  of  these  have  partially  coalesced.  They  are  dis- 
tinctly circumscribed  in  the  surrounding  tissues  ;  and  there  are  no  signs  of 
any  pedicles  connecting  them  with  the  wood  of  the  tree.  The  succeeding 
specimen  (No.  546s)  shows  a  similar  tumour  from  a  beech-tree,  also  devoid 
of  pedicle  ;  and,  in  No.  546D,  we  have  five  similarly  situated  tumours,  also 
from  a  beech-tree,  with  a  few  buds  projecting  from  their  surf  aces,  while  here 
and  there  some  of  these  buds  have  developed  shoots  or  minute  branches. 


TUMOURS  IN  VEGETABLE  ORGANISMS  121 

It  may  be  said  of  these  tumours,  that  they  usually  present  as  rounded 
or  ovoid  swellings  in  the  deeper  part  of  the  bark,  varying  in  size  from  a 
pin's  head  to  a  cocoanut  or  larger.  The  older  nodules  are  generally  found 
lying  completely  isolated  in  the  bark  ;  and  a  narrow  fibro- vascular  pedicle 
may  sometimes  be  seen,  connecting  the  younger  ones  with  the  woody 
tissues  of  the  trunk  or  stem.  When  the  pedicles  persist,  these  formations 
are  apt  to  become  included  in  the  woody  tissue  of  the  stem,  giving  rise 
to  the  so-called  "  knots  "  in  the  wood.  In  the  earlier  stages  of  their 
development,  these  tumours  are  occasionally  surmounted  by  a  small 
stunted  branch  or  shoot.  On  section,  they  are  found  to  consist  of  very 
dense  wood,  having  a  more  or  less  concentric  arrangement  around  one  or 
more  centres,  according  as  their  origin  is  from  single  or  multiple  buds. 
In  most  cases  both  pith  and  medullary  rays  can  be  made  out.  Not 
infrequently,  however,  their  internal  structure  is  much  more  irregularly 
disposed.  In  short,  they  comprise  all  the  structural  elements  of  the  part 
whence  they  spring, 'but  differently  arranged.  It  would  seem  as  if  they 
might  be  regarded  as  stunted  branches,  in  which  the  woody  layers  had  been 
abnormally  developed,  in  compensation  for  the  curtailment  in  length 
and  in  other  respects. 

Lying  at  first  isolated  in  the  bark,  these  nodules  increase  in  size  at 
the  expense  of  the  surrounding  nutritive  materials.  Hence,  it  often 
happens  that  their  growth  on  the  side  of  the  cambium  outruns  that  on 
the  other  side,  where  the  nutritive  supply  is  less  abundant,  so  that  a  certain 
eccentricity  in  the  arrangement  of  the  laminae  is  produced.  Destruction 
of  the  bark  which  usually  covers  them  in,  whether  as  the  result  of  injury 
or  some  other  cause,  such  as  pressure  of  the  growing  nodule  itself,  renders 
this  tendency  to  increased  growth  on  the  side  of  the  cambium  still  more 
marked  ;  for,  we  then  see  complete  cessation  of  growth  at  the  exposed  sur- 
face, which  may  even  decay  in  consequence,  while  the  side  of  the  nodule 
next  to  the  wood,  owing  to  the  proximity  of  the  cambium,  still  continues 
to  increase. 

These  tumours,  as  Dutrochet  long  ago  discovered,  first  appear  as  very 
small  buds  in  the  cellular  tissue  of  the  bark ;  where  they  originate  from 
unspecialized  cells,  quite  independently  of  the  wood  of  the  trunk.  In 
short,  almost  all  of  those  who  have  specially  studied  this  subject,  are  now 
agreed  in  ascribing  the  origin  of  these  tumours  to  disorderly  growth  of 
adventitious  or  dormant  buds.  There  is  no  doubt  that  buds  may  remain 
in  a  quiescent  state  for  years  ;  and  then,  under  the  influence  of  favourable 
conditions,  develop  renewed  activity,  the  result  being  either  a  shoot,  a 
branch,  or  one  of  these  tumours. 

Such  being  their  origin,  it  is  not  surprising  to  find  these  tumours,  like 
buds,  possessed  of  distinct  individuality  ;  and  capable  of  reproducing  their 
like  in  the  form  of  buds,  shoots,  branches  etc.  It  even  occasionally 
happens  that,  in  their  young  state,  these  anomalous  formations  may  be 
used  for  propagating  the  species  asexually. 

In  all  of  the  above  instances,  the  outcome  of  the  morbid  process  is  the 
production  of  a  highly  organized,  circumscribed,  new  formation,  analogous 
to  the  fibromas,  lipomas,  and  other  similar  non-malignant  new  growths 
of  human  and  animal  pathology. 


122  THE  NATURAL  HISTORY  OF  CANCER 

Before  entering  on  the  consideration  of  the  second  group  of  tumours 
in  trees,  I  must  first  of  all  offer  a  few  observations  with  regard  to  certain 
intermediate  formations  of  the  nature  of  local  overgrowths.  I  have  often 
remarked  in  various  trees  the  presence  of  hypertrophic  branches  ;  and,  in 
several  instances,  I  have  seen  localized  hypertrophies  involving  the  whole 
thickness  of  portions  of  the  branches  of  such  trees  as  the  elm,  lime,  and 
oak.  These  conditions  may  be  compared  with  the  hyperostoses  of 
human  pathology.  They  occupy  an  intermediate  position  between  the 
hypertrophic  and  neoplastic  processes.  Such  conditions  arise  at  an  early 
stage  of  development,  in  consequence  of  excessive  activity  of  the  cambium 
at  the  affected  part.  These  local  overgrowths  generally  present  as  elon- 
gated protuberances  covered  with  bark,  their  diameter  being  many  times 
greater  than  that  of  the  branch  or  stem  whence  they  grow.  On  section, 
they  consist  of  hard  wood,  the  concentric  layers  of  which  are  unusually 
thick  and  very  obvious,  while  the  medullary  rays,  extending  from  the 
centre  to  the  periphery,  are  but  thin.  Trecul  has  figured  a  fine  example 
of  this  kind  from  a  birch-tree. 

The  second  group,  comprising  the  continuous  tumours,  are  comparable 
with  the  exostoses  of  human  pathology.  These  present  as  woody  out- 
growths of  the  trunk  or  branch.  They  often  attain  great  size,  as  in  the 
specimen  figured  on  the  next  page  (Fig.  4),  which  measured  16  by  1 1  inches, 
and  weighed  67  pounds  :  the  diameter  of  the  branch  on  which  this  tumour 
grew,  was  4|  inches  on  the  proximal  and  4  inches  on  the  distal  side. 

The  general  characters  of  these  growths  may  be  gathered  from  the 
subjoined  brief  description  of  this  specimen,  which  was  removed  from  one 
of  the  largest  branches  of  a  young  elm-tree — probably  about  thirty-five 
years  old — on  the  main  trunk  of  which  was  another  similar  growth,  the 
tree  being  in  other  respects  healthy.  It  was  completely  covered  with 
rather  hypertrophied  bark,  and  two  small  branches  grew  from  its  surface 
near  the  periphery.  On  longitudinal  section,  it  was  found  to  consist  of 
very  hard  wood,  directly  continuous  with  that  of  one  side  of  the  branch 
whence  it  grew.  The  laminae  composing  the  tumour  showed  a  concentric 
arrangement  of  outcurved,  irregularly  wavy  layers  ;  Avhile  those  of  the 
branch  itself  appeared  longitudinal  (Fig.  4).  Moreover,  the  former  were 
many  times  thicker  than  the  latter  ;  and  in  the  broadest  part  of  the 
tumour  I  was  able  to  count  twenty-six  of  these  layers.  A  singular 
feature  in  this  case  is,  that  a  portion  of  the  tumour  had  grown  completely 
round  the  healthy  part  of  the  branch,  outside  the  bark ;  and  had  then 
blended  with  the  main  tumour  on  the  opposite  side,  so  as  completely  to 
encircle  the  branch  on  which  it  grew.  This  specimen  was  removed  from 
a  tree  growing  in  a  damp  meadow,  where  the  soil  was  heavy,  and  saturated 
with  sewage-polluted  water.  An  adjacent  elm,  of  about  the  same  size, 
presented  a  single  similar  outgrowth  on  its  main  trunk. 

Similar  tumour-like  growths  have  occasionally  been  seen  even  on  the 
root  of  various  plants — e.g.,  Taxodium  distichum,  Cupressus  macaro- 
carpa  etc. 

Dutrochet  describes  these  growths  as  arising  in  much  the  same  way 
as  the  discontinuous  knaurs,  by  a  kind  of  bud  formation,  in  the  deeper 
part  of  the  cambium  layer  ;  hence  their  connexion  with  the  woody  tissues 


TUMOURS  IN  VEGETABLE  ORGANISMS  123 

of  the  stem  is  well  secured  from  the  outset,  and  so  it  is  never  lost.  These 
tumours  may  be  regarded  as  stunted,  abnormally  evolved,  branches. 

Composite  tumours  of  this  kind,  resulting  from  a  group  of  buds — 
instead  of  a  single  one — being  concerned  in  the  origin  of  the  malady,  are 
by  no  means  unusual ;  and  thus  very  dense  formations  are  often  developed 
on  elm  stems,  which  are  in  much  demand  by  cabinet-makers,  on  account 
of  the  remarkable  patterns  presented  by  the  diversely  contorted  arrange- 
ment of  their  woody  fibres. 

Such  being  their  structure  and  mode  of  origin,  the  tumours  of  this 
group  may  fairly  be  compared  with  the  exostoses  and  analogous  con- 
tinuous tumours  of  human  pathology ;  and,  like  them,  they  are  highly 
organized. 


FIG.  4. — A  CONTINUOUS  TUMOUR — COMPARABLE  TO  AN  EXOSTOSIS — FROM  AN  ELM- 
TREE,  IN  LONGITUDINAL  SECTION.  , 

In  the  third  group,  I  include  all  those  new  formations,  called  by  the 
French  broussins,  whose  distinguishing  peculiarity  is  the  very  free  and 
continuous  formation  of  proliferous  buds,  shoots,  and  stunted  branches. 
The  term  "  burr  v  might  very  well  be  employed  as  the  English  synonym 
for  these  growths,  which  often  attain  enormous  proportions. 

I  have  seen  an  old  lime-tree,  with  a  huge  excrescence  of  this  kind 
densely  studded  with  buds,  shoots,  and  brushwood,  growing  at  the  junction 
of  the  trunk  with  the  main  branches.1 

Three  other  aged  lime-trees  in  the  immediate  vicinity  were  similarly 
affected.  In  all  of  these  cases,  the  general  health  of  the  trees  appeared  to 

1  This  growth  is  figured  in  my  book  on  "  The  Principles  of  Cancer  and  Tumour 
Formation,"  Fig.  15,  p.  98. 


124  THE  NATURAL  HISTORY  OF  CANCER 

have  deteriorated  considerably,  as  indicated  by  numerous  dead  branches, 
etc.  In  the  same  neighbourhood  I  have  seen  similar  growths  on  elm, 
hornbeam,  and  other  trees,  one  of  which  is  figured  on  the  next  page  (Fig.  5). 
The  trees  of  this  particular  locality  are,  in  fact,  remarkably  prone  to  these 
growths,  and  to  various  other  morphological  anomalies.  Most  of  these 
trees  are  old,  and  of  large  size.  For  a  long  period  they  have  been  left  quite 
uncared  for — innocent  of  the  acts  of  forestry.  The  situation  of  the 
locality  is  peculiar.  It  forms  part  of  a  shallow  depression,  lying  below  the 
slope  of  a  hill.  A  large  brook,  the  natural  watershed  of  the  neighbour- 
hood, runs  sluggishly  through  the  low-lying  part.  In  its  course,  it  here 
forms  several  large  lacustrine  ponds,  owing  to  the  slightness  of  the 
gradient.  The  water  is  highly  charged  with  sewage  matter.  Clay  for- 
mation underlies  the  whole  neighbourhood,  and  forms  the  bed  of  the 
watercourse,  while  a  layer  of  loose  gravel  rests  on  the  clay.  It  results 
from  this  arrangement,  that  the  whole  of  the  depressed  area  is  thoroughly 
saturated  with  sewage-contaminated  water ;  and  its  vegetation  has 
consequently  long  been  abnormally  nourished. 

A  specimen  illustrating  the  same  type  of  disease,  from  one  of  the  chief 
branches  of  a  hornbeam-tree,  is  shown  in  Fig.  5.  The  growth  is  composed 
of  innumerable,  densely  massed  buds,  a  few  of  which  have  developed  into 
shoots  and  twigs.  Almost  the  whole  circumference  of  the  branch,  for  a 
distance  of  15  inches,  is  surrounded  by  the  growth.  On  section,  the 
subjacent  woody  tissue  of  the  branch,  corresponding  to  the  seat  of  the 
disease,  is  seen  to  be  double  its  normal  thickness.  The  wood  here  is  very 
dense  and  of  irregular  formation,  except  in  the  central  part ;  and,  between 
the  two,  there  is  no  definite  line  of  demarcation.  Interspersed  in  this 
dense  wood  are  detached  fragments  of  bark ;  and,  in  several  places,  long 
processes  of  bark  penetrate  deeply  into  the  wood.  This  great  thickening 
and  irregular  formation  of 4 the  wood,  are  due  to  the  exuberant  and' 
irregular  flow  of  sap,  caused  by  the  abnormal  and  proliferous  gemmation, 
which  is  the  essential  element  of  the  disease. 

I  have  seen  similar  tumours  on  elm  and  other  trees. 

The  peculiarity  of  growths  of  this  kind,  consists  in  the  immense  number 
of  buds  which  develop  adventitiously  in  the  cambium  layer  of  the  affected 
part ;  when,  they  either  remain  dormant,  or  forthwith  develop  into  shoots 
or  stunted  branches.  The  aggregation  of  these  structures  causes  retar- 
dation and  irregularity  in  the  flow  of  the  sap  ;  whence  the  exuberance  of 
the  growth,  and  the  curious  markings  produced  in  the  wood.  Moquin- 
Tandon  mentions  having  seen  a  grafted  ash,  in  the  Botanical  Garden  of 
Toulouse  ;  where,  below  the  graft,  a  large  growth  of  this  kind  formed, 
from  which  proceeded  over  a  thousand  small,  densely  packed  interlacing 
branches. 

The  production  by  these  growths  of  large  quantities  of  proliferous, 
lowly  organized,  cellular  tissue,  which  subsequently  undergoes  some 
imperfect  developmental  changes — mimicking  the  structure  of  the  part — 
constitutes  the  nearest  approach  in  vegetable  pathology  to  the  malignant 
tumours  of  human  and  animal  pathology.  The  absence  in  these  vegetable 
tumours  of  anything  like  the  disseminativeness  of  human  malignant 
tumours,  may  be  urged  as  an  objection  to  this  comparison.  But  to  this 


TUMOURS  IN  VEGETABLE  ORGANISMS 


125 


the  answer  is,  that  in  the  absence  of  a  highly  specialized  lymph-vascular 
system,  capable  of  transporting  the  proliferous  cells,  such  disseminative- 
ness  is  not  to  be  expected ;  and  that  it  is  to  deficiency  in  this  respect — 
rather  than  to  any  essential  difference  in  the  nature  of  the  morbid  process 
— that  the  absence  of  disseminativeness  in  vegetable  tumours  must  be 
ascribed.  For,  as  I  have  previously  indicated,  the  essential  feature  of 
malignancy  is  not  disseminativeness,  but  rather  the  indefinitely  sustained 
activity  of  certain  lowly  organized  cells,  which  grow  and  multiply 
independently,  without  ever  reaching  the  highest  grade  of  organization. 


FIG.  5. — A  MALIGNANT  TUMOUR,  DENSELY  STUDDED  WITH  SHOOTS  AND  STUNTED 
TWIGS,  FROM  ONE  OF  THE  CHIEF  BRANCHES  OF  A  HORNBEAM- TREE. 

With  regard  to  the  aetiology  of  these  growths,  beyond  what  has  been 
above  indicated,  all  that  I  need  now  say  is,  that  I  have  been  unable  to  find 
any  evidence  as  to  their  being  due  to  parasites  or  other  irritants  ab  extra. 


Galls  and  Other  Vegetable  Pseudo-plasms. 

Even  in  human  and  animal  pathology  it  cannot  be  denied,  that 
irritative  conditions  may  elicit  formative  reactions  ;  and,  in  the  vegetable 
world,  even  among  highly  evolved  forms,  reactions  of  this  kind  are  of 
frequent  occurrence  as  well  as  of  marked  character.  This  is  exemplified  in 


126  THE  NATURAL  HISTORY  OF  CANCER 

the  case  of  galls,  which  may  comprise  not  only  structures  similar  to  those 
met  with  in  the  parts  whence  they  originate,  but  also  other  structures 
which  do  not  occur  there  ;  thus,  as  Beyerinck  has  shown,  cells  which  are 
usually  only  developed  in  the  bark,  are  frequently  found  in  some  leaf- 
galls  etc. 

The  formation  of  galls  is  certainly  a  very  interesting  phenomenon, 
which  has  yet  to  be  fully  explained,  as  have  also  the  analogous  processes 
underlying  bud,  cancer  and  tumour  formation,  and  other  morphological 
variations. 

It  was  formerly  thought  that  galls  arose  in  consequence  of  excessive 
local  cell  growth  and  proliferation,  excited  by  a  virus  instilled  into  wounds 
made  by  insects  in  depositing  their  ova  ;  but  the  researches  of  Adler  and 
Beyerinck  have  shown  the  inadequacy  of  this  conception.  They  have 
conclusively  proved  that  galls  are  due,  not  to  the  sting  of  the  parent 
insect,  but  to  the  activity  of  the  larva  after  it  has  been  hatched. 

Although  most  gall-producing  insects  do  actually  wound  the  tissues  of 
plants  in  depositing  their  ova,  yet  no  galls  result  from  the  lesions — for 
instance,  in  the  case  of  the  common  oak-apple  gall,  the  Biorhiza  aptera 
deposits  its  ova  in  punctures  in  the  bud  early  in  the  winter,  but  no  gall 
formation  occurs  until  the  following  spring,  when  the  larvae  become 
active  ;  similarly,  when  no  ova  are  deposited  in  the  punctures  made  by 
the  parent  insect,  no  gall  is  formed  ;  and  the  result  is  just  the  same  when, 
although  ova  have  been  deposited,  the  embryos  fail  to  develop  or  die 
early  ;  and,  when  the  larva  dies,  the  gall  ceases  to  grow.  From  these 
considerations  it  follows  that  the  gall  is  the  reaction  of  the  plant  to  some 
X  stimulus  proceeding  from  the  larva,  the  nature  of  which  is  still  under 
discussion. 

It  is  hardly  likely  that  the  mere  presence  of  the  larva,  acting  as  a 
foreign  body,  or  its  movement^  per  se,  can  be  the  real  causative  factors  of  , 
these  formations,  otherwise  there  would  not  be  such  extraordinary 
diversities  in  the  resulting  galls — those  produced  by  the  larva  of  each  kind 
of  insect  presenting  structural  peculiarities  which  are  quite  sui  generis. 
Thus,  on  the  oaks  of  Central  Europe  alone,  nearly  a  hundred  different 
kinds  have  been  discriminated,  all  produced  by  different — but  closely 
allied — species  of  gall  wasps. 

Of  like  import  is  the  fact,  that  no  one  has  yet  succeeded  in  producing 
galls  experimentally,  although  attempts  of  this  kind  have  not  been  lacking. 

Another  indication  pointing  in  the  same  direction  comes  from  Adler 's 
interesting  discovery,  that  galls  produced  by  the  same  insect,  in  the 
alternating  phases  of  its  heterogenesis,  are  markedly  different  :  thus,  the 
-^  common  currant  gall  of  the  male  flower  of  the  oak,  is  the  product  of  one 
phase  (unisexual)  of  the  existence  of  a  gall-producing  insect,  which  in 
another  phase  (bisexual)  causes  the  red  spangle  gall  of  the  under  surface 
of  the  oak  leaf. 

It  seems  to  follow  from  these  considerations,  that  the  stimulus  in 
question  must  be  some  specific  secretion  of  the  larvae  themselves  ;  and 
Beyerinck  considers  that  the  salivary  secretion  is  the  one  specially 
indicated,  the  active  principle  perhaps  being  some  special  fermentative 
or  allied  bio-chemical  process,  not  as  yet  discriminated.  However  this 


TUMOURS  IN  VEGETABLE  ORGANISMS  127 

may  be,  it  is  evident  that -very  slight  differences  in  the  nature  of  the 
causative  stimulus,  determine  widely  different  morphological  results  in 
the  produced  gall ;  this  is  specially  obvious  when,  as  sometimes  happens, 
several  quite  different  galls,  caused  by  as  many  different  parasites,  are 
formed  on  the  same  leaf. 

In  discussing  this  subject,  Darwin  remarks  :  "As  the  poisonous 
secretion  of  insects  belonging  to  various  orders,  has  the  special  power  of 
affecting  the  growth  of  various  plants  ;  as  a  slight  difference  in  the  nature 
of  the  poison  suffices  to  produce  widely  different  results  ;  and,  lastly,  as 
we  know  that  the  chemical  compounds  secreted  by  plants  are  eminently 
liable  to  be  modified  by  changed  conditions  of  life,  we  may  believe  it 
possible  that  the  various  parts  of  a  plant  might  be  modified  through  the 
agency  of  its  own  altered  secretions.  With  such  facts  before  us,  we  need 
feel  no  surprise  at  the  appearance  of  any  modification  in  any  organic 
being." 

As  exemplifying  these  remarks,  we  may  profitably  recall  and  contrast 
the  mossy  rose-gall,  the  product  of  extrinsic  parasitic  stimulation  ;  and 
the  mossy  outgrowths  of  the  calyx  of  the  moss  rose,  spontaneously  arising 
as  the  result  of  unknown  intrinsic  changes. 

.   The  willow  galls — caused  by  a  species  of  Nematus — also  illustrate  the 
free  formation  of  epidermal  trichomes,  in  response  to  parasitic  irritation. 

Another  remarkable  feature  about  such  galls  as  we  are  now  concerned 
with  is,  that  the  form  assumed  by  them  is  "beneficial  to  the  parasite  rather 
than  to  the  tree-host ;  so  that  it  appears  as  if  we  must  ascribe  this  effect 
to  a  specific  stimulus  proceeding  from  the  larva,  which  these  formations 
are  obviously  adapted  to  protect,  support,  and  nourish  ;  and  it  is  difficult 
to  escape  the  conclusion,  that  this  stimulation  is  in  some  way  connected 
with  the  feeding  of  the  larva  on  the  cells  of  the  plant  by  which  it  is  sur- 
rounded. As  for  the  reaction  on  the  part  of  the  tree-host,  this  may  be 
regarded  as  an  exaggerated  and  specifically  modified  outcome  of  the 
reparative  process.  Some  remarkable  examples  of  the  influence  of  the 
stimulus  in  directing  this  reaction  for  the  advantage  of  the  parasite,  are 
seen  in  the  case  of  those  galls  out  of  which  the  parasite  is  unable  to  eat 
its  way,  when  the  time  for  escape  has  come ;  for  such  galls  then  dehisce, 
as  many  fruits  do,  and  so  allow  the  parasite  to  escape. 

In  this  connexion,  however,  it  should  be  noted  that  among  the  immense 
number  of  galls,  there  are  some  in  which  host  and  parasite  live  together  in 
a  manner  that  is  mutually  beneficial  (symbiosis) ;  while,  in  others,  the  joint 
existence  is  very  harmful  or  even  fatal  to  the  plant-host. 

As  an  example  of  the  former  condition,  the  remarkable  growths 
occasioned  by  parasitic  ants,  in  the  so-called  "  ant  plants  "  (Myrmecodia 
etc.),  may  be  cited  ;  which  Beccari  and  others  consider  to  be  indispensable 
for  the  healthy  development  of  such  plants — the  latter  protecting  the 
ants,  which  in  their  turn  protect  the  plant. 

In  like  manner  the  galls  formed  on  the  roots  of  leguminous  plants, 
owing  to  the  agency  of  parasitic  fungi,  contribute  to  the  well-being  of 
the  plant,  by  elaborating  and  storing  nutritive  materials  for  its  use. 

In  these  cases,  we  have  evidence  that  plants  subjected  to  certain 
stimuli  of  vital  origin  respond  thereto,  not  merely  by  local  hypertrophy, 


128  THE  NATURAL  HISTORY  OF  CANCER 

but  also  by  profound  alterations  in  their  morphological  and  physiological 
dispositions,  which  ordinary  mechanical  stimuli  are  unable  to  elicit. 

The  earliest  changes  in  gall-formation  consist  in  active  growth  and 
proliferation  of  the  merismatic  cells — "  blastem  " — immediately  sur- 
rounding the  parasitic  embryo  ;  these  cells  from  the  first  respect  the 
included  larva,  for  which  in  the  course  of  their  subsequent  development 
a  free  cavity  is  formed — the  so-called  larval  chamber  ;  and  they  subse- 
quently undergo  developmental  differentiation,  much  after  the  manner 
proper  to  the  normal  ontogeny  of  the  affected  part. 

It  is  a  noteworthy  fact  that  some  galls,  like  abnormally  evolving 
adventitious  buds,  may  be  used  for  purposes  of  propagation. 

Gall-producing  parasites  are  exceedingly  numerous  and  of  many 
diverse  kinds,  both  animal  and  vegetable  forms  being  represented ;  but 
the  commoner  and  more  conspicuous  galls  are  generally  caused  by  insecta 
— most  orders  of  this  class  comprising  some  gall-producing  representa- 
tives, of  which  CynipidoB  and  Acari  are  among  the  commonest ;  fungi  are 
also  responsible  for  many — e.g.,  the  "  apple  canker,"  due  to  Nectria 
ditissima  ;  and,  besides  these,  various  protophyta  and  protozoa,  such  as 
the  Plasmodiophora  brassicce,  which  cause  the  tumour-like  swellings  on 
the  roots  of  cabbages  etc. 


CHAPTER  VII 
THE  GENESIS  OF  MALIGNANT  TUMOURS 

Historical  Review. 

THE  ancients  of  the  classical  period  divided  tumours  into  three  great 
classes  :  Tumores  secundum  naturam,  supra  naturam,  prceter  naturam. 
Physiological  enlargements  were  included  in  the  first ;  the  second  com- 
prised swellings  due  to  the  displacements  of  natural  parts  ;  while  the 
third  embraced  all  other  swellings — a  miscellaneous  assemblage,  com- 
prising all  that  we  now  include  under  the  term  "  tumour,"  and  many 
other  conditions  besides. 

By  Galen  l  and  his  followers  the  tumours  prceter  naturam  were  believed 
to  result  from  the  accumulation  of  one  or  other  of  the  four  humours,  each 
of  which  generated  its  corresponding  kind  of  tumour.  Of  these  humoral 
tumours,  those  of  the  group  called  "  scirrhous  " — which  embraced  cancer, 
and  nearly  corresponded  with  that  we  now  understand  by  the  word 
"  tumour  " — were  believed  to  arise  from  the  accumulation  of  atrabile 
(Cancer  ab  atrabile). 

After  the  long  centuries  of  ignorance,  stagnation  and  superstition, 
that  followed  the  overthrow  of  the  Roman  Empire  and  classical  learning, 
by  swarms  of  barbarian  warriors,  the  humoral  theory  at  length  emerged 
from  the  wreck  not  appreciably  altered.2 

Indeed,  it  was  not  until  the  discovery  of  the  circulation  of  the  blood, 
early  in  the  seventeenth  century  (Harvey,  Malpighi,  Leeuwenhoek,  and 
others),  that  this  doctrine  was  overturned. 

In  place  of  the  humours,  the  blood  was  now  regarded  as  the  true  source 
of  the  disease. 

Early  in  the  eighteentli  century  the  Cartesians,  with  Boerhaave  at 
their  head  (Morbus  est  vita  prceter  naturam),  ascribed  the  origin  of 
tumours  to  the  newly  discovered  lymph — a  derivative  of  the  blood  : 
cancer  they  regarded  as  the  outcome  of  vitiated,  depraved,  or  degenerated 
lymph. 

Doctrines  of  this  kind  continued  to  hold  sway,  until  the  time  of  Bichat 
— at  the  end  of  the  eighteenth  century. 

With  the  advent  of  the  illustrious  founder  of  biology,  we  begin  to 
discern  the  first  rudiments  of  modern  conceptions  emerging  from  the 
ancient  chaos.  The  philosophical  insight  of  Bichat  enabled  him — 

"  De  tumoribus  prseter  naturam." 

2  As  a  historian  of  medicine  has  remarked  :  "  Greek  medicine  of  the  fifth  century  B.C. 
seems  to  be  almost  of  yesterday  ;  whereas,  English  medicine  of  the  twelfth  century  of 
our  era,  is  as  alien  and  grotesque  to  our  thought  as  the  demonology  of  the  Chaldeans." 

129  9 


130  THE  NATURAL  HISTORY  OF  CANCER 

without  the  aid  of  the  microscope  and  relying  only  on  gross  appearances — • 
to  decompose  the  organism  into  its  elementary  tissues '  and  organic 
systems.  "  Every  tissue,"  said  Bichat,  "  has  its  own  diseases." 

This  was  a  great  advance  on  previous  ideas ;  and  it  is  on  this  basis 
that  the  modern  anatomico-pathological  study  of  tumours  rests,  which 
the  labours  of  Laennec,  Andral,  Louis,  Bayle  and  Cruveilhier  in  the  same 
direction  subsequently  strengthened  and  extended. 

Thus  Bichat  anticipated  and  prepared  the  way  for  the  cell  theory — 
the  culminating  point  of  modern  biological  progress — although  due 
acknowledgment  of  this  his  great  achievement  has,  I  think;  never  before 
been  accorded  to  him  by  English,  American,  or  German  pathologists. 

At  this  juncture,  early  in  the  nineteenth  century,  the  current  of 
thought  was  suddenly  interrupted  and  changed,  by  the  appearance  on 
the  scene  of  the  impetuous  Broussais.1  His  doctrine  was  that  all  tumours, 
including  cancers,  wrere  but  forms  of  chronic  inflammation,  consequent  on 
organic  irritation.  The  extreme  simplicity,  comprehensiveness,  and 
positiveness  of  this  crude  generalization — suddenly  sprung  on  a  scientific 
world,  hesitating  between  the  old  humoral  doctrines  and  the  nascent 
anatomico-pathological  tentatives — captivated  every  one ;  and  the 
Broussaisian  system,  in  an  incredibly  short  time,  became  supreme. 

But  its  supremacy  was  short-lived.  What  more  than  anything  else 
contributed  to  its  downfall,  was  the  application  of  the  microscope  to  the 
study  of  living  things.  To  this  instrument  and  its  revelations,  we  are 
indebted  for  the  two  great  doctrines  of  modern  medical  science — the 
cell  theory  and  the  germ  theory.  The  far-reaching  importance  of  the 
revolution  thus  effected  is,  even  now,  by  no  means  duly  appreciated. 
It  might  be  thought  that  the  history  of  the  invention  of  an  instrument, 
which  has  done  so  much  to  enlarge  the  field  of  knowledge  as  the  micro- 
scope, would  be  a  theme  for  every  one  ;  but,  as  a  matter  of  fact,  the 
discovery  is  shrouded  in  obscurity.  It  is  believed  that  the  earliest 
compound  microscope  was  made  by  the  Janssens— father  and  son— 
spectacle-makers  of  Middelburg  in  Holland,  near  the  end  of  the  sixteenth 
century.  One  of  their  instruments  was  exhibited  in  London — by  Drebbel 
of  Alkmaar — early  in  the  seventeenth  century  (1617).  Unfortunately  it 
was  imposible  to  see  clearly  with  this  instrument,  when  high  magnifying 
powers  were  used,  owing  to  the  disturbing  influences  of  chromatic  and 
spherical  aberration  ;  hence  the  compound  microscope  was  at  first  merely 
a  scientific  toy.  It  took  more  than  two  centuries  to  overcome  these 
defects.  At  length,  early  in  the  nineteenth  century — thanks  to  the  skill 
of  Selligues,  Chevalier,  Tully,  Amici,  Lister,  and  others — these  difficulties 
were  surmounted.  In  1830,  a  real  serviceable  compound  microscope  was 
at  last  produced  ;  and  with  its  aid  naturalists,  shortly  afterwards,  began 
to  explore  the  minute  structure  of  organic  forms,  as  Newton  had  long 
before  predicted.  Thus  the  science  of  histology  was  born,  which 
subsequent  improvements  in  optical  appliances  and  a  better  technique, 
have  advanced  to  its  present  remarkable  state  of  perfection. 

With  this  new  aid  the  cellular  structure  of  organized  beings  was  ere 
long  discovered.  For  the  famous  cell  theory — which  must  be  ranked 
1  "  Traite  des  Phlegmasies  chroniques,"  1808,  etc. 


THE  GENESIS  OF  MALIGNANT  TUMOURS  131 

among  the  most  important  steps  by  which  the  science  of  biology  has 
ever  been  advanced — we  are  indebted  to  the  vegetable  morphologist 
Schleiden  ;  and  shortly  afterwards  Schwann  demonstrated  the  applica- 
bility of  his  generalizations  to  the  animal  world  (1838).  In  the  very  same 
year  the  publication  of  J.  Miiller's  important  work  on  the  origin  of 
tumours,1  established  the  cellular  nature  of  cancer  and  other  neoplasms. 
Modern  conceptions  as  to  the  pathogenesis  of  tumours  date  from  this 
period. 

Miiller  believed  that  the  constituent  cells  of  tumours  were  derived 
from  a  formative  fluid,  exuded  from  the  blood  (blastema) ;  which  was 
nothing  but  the  coagulable  lymph  of  Hunter,  under  another  name.  He 
ascribed  the  origin  of  cancer  and  other  neoplasms,  and  their  variations 
inter  se,  to  aberrations  of  the  force  inherent  in  this  primordial  substance, 
causing  the  resulting  cells  to  deviate  from  their  usual  evolution.  Miiller 
also  strongly  insisted  on  the  correspondence  between  the  development 
from  the  embryo,  and  the  pathological  neoplastic  process  :  "  It  is  one 
and  the  same  power  which,  being  maintained  continuously  from  the  germ 
to  the  latest  period  of  life,  determines  all  organic  formation." 

The  pathological  cells,  he  maintained,  differed  from  the  physiological 
cells  only  in  respect  to  the  degree  of  evolution  ultimately  attained.  The 
division  of  neoplasms  into  two  great  classes,  according  as  their  structure- 
resembled  the  normal  tissues  (homologous),  or  differed  from  them 
(heterologous),  Miiller  completely  rejected.  "  It  is  evident,"  he  says, 
"  that  no  division  of  pathological  structures  into  homologous  and  hetero- 
logous can  be  established.  Such  a  classification  is  formed  without  anv 
knowledge  of  the  structure  of  morbid  growths.,  and  is  founded  on  blind 
gratuitous  hypothesis.  The  most  innocent  growths  do  not  differ  in  their 
minute  elements,  nor  in  their  origin,  from  the  most  malignant  ones." 

The  establishment  of  the  cell  theory  gave  an  immense  impetus  to 
pathological  histology,  and  a  vast  mass  of  new  data  soon  accumulated. 
Virchow,2  some  twenty  years  later,  pounced  upon  these ;  and,  with 
wonderful  insight,  skill,  and  energy,  elaborated  them,  together  with 
independent  observations,  into  a  kind  of  new  cell  theory ,.  which  still 
prevails.  Virchow's  influence  on  modern  conceptions  has  been  so  great, 
that  it  will  be  of  interest  to  trace  the  genetic  relationship  of  his  ideas  with 
those  of  his  predecessors.  It  may  be  said  that  he  adopted  the  cell  theory 
in  its  entirety,  as  laid  down  by  Miiller,  with  the  single  important  excep- 
tion, that  he  completely  exorcised  the  blastemal  origin  of  cells.  It  was 
just  this  omission  that  chiefly  constituted  the  novelty  of  his  system. 
Instead  of  a  hypothetical  blastema,  he  substituted  the  famous  formula 
''  Omnis  cellula  &  celluld"  =  "  Where  a  cell  arises  there  a  cell  must  have 
previously  existed,  just  as  an  animal  can  spring  only  from  an  animal, 
and  a  plant  from  a  plant."  Thus  the  doctrine  of  continuous  cellular 
development,  that  had  been  established  by  Remak  for  the  normal  tissues, 
became  the  basis  of  Virchow's  neoplastic  pathogeny. 

Another  important  respect  in  which  Virchow's  cellular  pathology  of 
tumours  differs  from  that  of  his  predecessors,  is  in  the  addition  to  it  of 

1  "  Ueber  den  feineren.  Bau  und  Formen  der  krankhaften  Geschwiilste,"  1838. 

2  "  Cellular  Pathologic,"  1859. 

9—2 


132  THE  NATURAL  HISTORY  OF  CANCER 

the  whijom  extinct  Broussaisian  doctrine  of  irritation  and  chronic 
inflammation.1  Nowhere  in  Virchow's  works  have  I  met  Avith  any  attempt 
to  explain  the  compatibility  of  this  irritation  hypothesis,  with  the  doctrine 
he  also  adopted,  of  the  correspondence  between  the  embryonic  and  neo- 
plastic  developmental  processes.  In  my  opinion,  these  views  are  abso- 
lutely incompatible ;  and  this  incompatibility  constitutes  a  serious  flaw 
in  Virchow's  neoplastic  pathogeny.  I  believe  that  tumour  formation  is 
the  outcome  of  formative  hyperplasia  (e.g.,  growth),  and  not  of  inflam- 
mation. By  most  pathologists  these  two  fundamentally  distinct  processes 
are  confused  together,  and  treated  as  being  one  and  the  same  ;  whereas, 
my  belief  is,  that  they  are  in  every  respect  different  and  distinct.  Inflam- 
mation is  the  outcome  of  extrinsic  causes  ;  whereas,  the  causes  which  deter- 
mine neoplastic  hyperplasia  are,  as  I  shall  show  in  the  sequel,  mainly 
intrinsic.  Moreover,  the  two  processes  are  morphologically  distinct. 
In  short,  the  morphological  and  biological  characters  of  tumours  show, 
that  neoplastic  pathogenesis  is  something  quite  different  and  distinct 
from  all  inflammatory  processes.  As  Billroth  has  remarked,2  if  we  once 
allowed  the  principle  of  the  correspondence  between  the  embryonic  and 
neoplastic  processes  to  be  lost  sight  of,  we  should  necessarily  fall  back 
"  into  the  old  chaos  of  parasites  and  pseudo-plasms,"  which  is  exactly 
what  we  are  now  experiencing. 

Of  late,  owing  to  a  variety  of  causes,  Virchow's  doctrines  have 
undoubtedly  lost  ground.  For  this  lapse,  Virchow  himself  is  to  a  large 
extent  responsible.  As  is  well  known,  his  dogmatical  and  didactic  mind 
entertained  deeply  rooted  aversion  for  all  kinds  of  theories  and  hypotheses. 
It  was  this  lack  of  scientific  imagination,  that  caused  him  to  go  out  of  his 
way,  in  a  realty  extraordinary  manner,  to  prevent  his  followers  from 
assimilating  the  new  facts  and  principles  brought  to  light  by  modern 
biological  progress,  in  connexion  with  the  doctrine  of  evolution.  Another 
consideration  that  tended  to  confirm  him  in  this  opposition,  was  the  fact 
that  in  the  domain  of  neoplastic  pathology,  wherein  his  ideas  concentred, 
evolutional  conceptions  seemed  to  have  but  little  application  ;  for  most 
pathological  neoplastic  phenomena  are  the  outcome  of  the  failure  or 
undoing  of  evolution.  Hence,  while  the  rest  of  biology  has  been  revo- 
lutionized, the  cellular  pathology  has  remained  stationary. 

So  far  as  the  pathology  of  neoplasms  is  concerned,  in  my  work  on 
"  The  Principles  of  Cancer  and  Tumour  Formation  "  (1888),  I  endeavoured 
to  repair  Virchow's  error,  by  laying  the  foundation  of  a  modified  cellular 
pathology  in  harmony  with  modern  biology  ;  and — although  this  \vork  has 
hitherto  received  no  recognition  from  contemporary  pathologists,  pre- 
occupied with  various  kinds  of  will-o'-the-wisps — I  confidently  look 
forward  to  the  time  when  the  conceptions  there  embodied  will  be  generally 
accepted,  as  furnishing  the  only  really  scientific  basis  for  explaining  the 
phenomena  of  pathological  neoplasia  ;  which,  as  I  have  there  set  forth,  is 
at  the  bottom  essentially  a  biological  problem.  Hence,  nothing  will  be 
more  conducive  to  this  end,  than  the  wider  spread  of  biological  knowledge 
and  conceptions  among  modern  pathologists  ;  who  are,  even  now,  for  the 

1  "  Die  krankhaften  Geschwiilste,"  Bd.  i.,  1863  (third  lecture). 

2  "Surgical  Pathology,"  1879,  p.  600. 


THE  GENESIS  OF  MALIGNANT  TUMOURS  133 

most  part,  very  deficient  in  this  respect,  as  so  many  recent  publications 
testify. 

Another  circumstance  that  has  tended  to  weaken  Virchow's  authority, 
is  the  large  measure  of  success  accorded  to  a  modification  of  the  cellular 
theory  propounded  by  Cohnheim,1  according  to  which  tumours  are  derived 
from  displaced  fragments  of  the  germinal  matrix,  sequestered  during  the 
earliest  period  of  embryonic  life. 

In  this,  its  original  primitive  form,  the  theory  was  only  capable  of 
very  limited  application  ;  but,  as  subsequently  modified,  so  as  to  include 
sequestrations  of  the  various  tissues  and  organs  arising  at  later  periods  of 
embryonic  ,and  post-embryonic  life  ("  rests  ").,  it  embraces  a  very  large 
number  of  facts  relating  to  tumour  genesis. 

Moreover,  in  this  way  attention  was  directed  to  the  frequent  association 
of  tumour  formation  with  various  kinds  of  developmental  irregularity — a 
very  important  indication. 

That  a  considerable  proportion  of  malignant  and  non  -  malignant 
tumours  actually  do  arise  in  this  connexion,  I  have  convinced 
myself. 

There  are,  in  fact,  good  reasons  for  believing — as  I  shall  presently 
show — that  tumours  are  specially  apt  to  arise  wherever  cells,  still  capable; 
of  growth  and  development,  are  present ;  and,  that  they  are  most  prone 
to  originate,  where  such  cells  most  abound. 


The  Present  Controversy. 

But  what  more  than  any  other  recent  occurrence,  has  undermined  the 
authority  of  the  cellular  neoplastic  pathogeny  is  the  widespread  belief, 
that  tumours  will  ultimately  turn  out  to  be  of  microbic  origin.  In  short, 
it  is  evident,  that  out  of  the  confusion  of  a  transitional  period,  but  two 
conceptions  as  to  the  origin  of  tumours  have  emerged — the  one  based  on 
the  cell  theory,  and  the  other  on  the  microbe  theory  ;  and  henceforth  the 
struggle  must  be  between  these  two.  Briefly  stated,  the  question 
now  is  :  Do  cancers  and  other  tumours  arise  through  modification 
of  the  formative  process.;  or,  are  they  the  outcome  of  the  inflamma- 
tory process,  owing  to  the  intrusion  of  microbes,  or  other  irritants 
ab  extra  ?  In  other  words  :  Are  they  essentially  of  intrinsic  or  extrinsic 
origin  ? 

Those  who  incline  to  the  former  alternative,  look  to  the  biological 
properties  of  the  cells  of  the  affected  part,  for  the  key  of  the  problem  : 
whereas,  the  other  side,  refer  all  the  essential  phenomena  of  the  disease  to 
the  activity  of  parasitic  microbes,  or  other  external  irritants. 

When  the  issues  are  thus  plainly  stated,  the  great  importance  of 
choosing  a  working  hypothesis  at  once  becomes  apparent ;  for,  of  the 
two  alternatives,  only  one  can  be  true.  My  own  belief  is,  that  tumours 
arise  mainly  from  the  abnormal  play  of  forces  generated  within  the  body  ; 
and  it  is  to  this  aspect  of  the  question  that  I  now  propose  to  direct 
attention. 

1  "  Vorlesungen  iiber  allgemeine  Pathologic,"  1877. 


134  THE  NATURAL  HISTORY  OF  CANCER 

The  General  Theory  of  Intrinsic  Pathogenesis. 

It  has  hitherto  been  customary,  as  I  have  previously  intimated,  to 
regard  tumour  formation  as  an  isolated  pathological  entity,  having  no 
connexion  with  other  biological  processes.  This  seems  to  me  to  be  a 
fundamental  mistake  ;  for,  the  first  step  towards  a  rational  interpretation 
of  tumour  genesis  from  the  biological  standpoint,  must  necessarily  be  the 
discovery  of  its  true  affinity.  Now,  it  is  in  morphological  variation  in 
general,  as  I  have  previously  indicated,  that  this  affinity  is  to  be  found. 
Indeed,  what  is  variation  but  a  novel  kind  of  cell  multiplication  ?  And 
what  is  tumour  formation  but  a  special  variety  of  this  novelty  ?  And  is 
not  every  variation,  as  Virchow  suggested,  essentially  pathological  ? 
The  answer  to  all  these  queries — as  we  now  see — is,  as  implied.  Variation, 
<  mutation,  and  tumour  formation,  these  are  but  different  manifestations 
of  one  and  the  same  process. 

In  the  preceding  chapter,  I  have  traced  the  connexion  between  these 
kindred  manifestations,  as  it  occurs  in  vegetable  organisms  ;  where 
tumour  formation  was  shown  to  be  an  outcome  of  abnormal  gemmation, 
which  is  a  form  of  agamogenesis. 

In  human  and  animal  organisms,  the  biological  significance  of  tumour 
formation  is  precisely  the  same,  as  I  have  shown  at  some  length  in  my 
book  on  "  The  Principles  of  Cancer  and  Tumour  Formation." 

In  that  work  I  have  adduced  reasons  for  believing,  that  there  is  no 
fundamental,  specific  distinction  between  such  apparently  varied  bio- 
logical processes,  as  the  various  modes  of  reproduction — gamogenetic  and 
agamogenetic,  the  processes  of  repair,  maintenance  and  new  formation 
of  tissues,  the  reproduction  of  lost  parts,  and  the  various  morphological 
variations — including  bud,  cancer  and  tumour  formations. 

All  of  these  apparently  so  different  phenomena,  are  there  shown  to  be 
merely  protean  modifications  of  one  common  process,  which  underlies  and 
is  the  cause  of  them  all — to  wit,  cell  growth  and  proliferation.  The 
particular  outcome  of  the  process  in  any  given  case,  is  shown  to  be  due  to 
the  influence  of  the  conditions  of  nutrition — understanding  by  this  term 
the  whole  of  the  material  changes  wrought  in  the  organism  through  its 
relations  with  the  surrounding  outer  world.  This  being  so,  it  is  easy  to 
understand  how,  under  favourable  conditions,  certain  cells  may  take  on 
independent  action,  growing  and  multiplying,  without  regard  to  the 
requirements  of  adjacent  tissues,  and  of  the  organism  as  a  whole.  Thus 
the  various  pathological  new  formations  arise.  From  the  biological 
standpoint,  then,  tumour  formation  must  be  regarded  as  a  phenomenon 
of  the  same  order  as  reproduction  in  general ;  that  is  to  say,  as  a  special 
form  of  overgrowth  of  the  individual. 

The  nearest  congeners  in  the  biological  domain  to  the  tumours  of 
human  and  animal  pathology,  must  be  sought  in  the  suddenly  occurring, 
non-adaptive  new  formations,  known  to  biologists  as  "  sports,"  "  bud 
variations,"  "  spontaneous  variations,"  "  discontinuous  variations,"  etc., 
all  of  which  abrupt  transformations  may  be  conveniently  comprised  under 
7  the  term  "  mutation,"  as  suggested  by  De  Vries.1 

1  Although  the  term  "  mutation  "  belongs  to  De  Vries,  the  mutation  theory  was 
founded  by  Bateson  ("  Variation,"  1894). 


THE  GENESIS  OF  MALIGNANT  TUMOURS  135 

Moreover,  all  of  these  kindred  processes  may  be  regarded  as  being 
dominated  by  a  common  aetiological  factor,  since,  in  ultimate  analysis, 
they  may  be  ascribed  to  the  cumulative  effects  of  changed  conditions  of 
existence — of  which,  in  the  case  of  animals,  the  most  important  items 
probably  are  excess  of  food,  changed  environment,  and  want  of  proper  * 
exercise. 

Another  question  of  fundamental  importance  remains  to  be  con- 
sidered, before  we  can  proceed  to  the  study  of  the  process  of  tumour 
genesis  ;  and  this  is  the  question  as  to  the  relations  of  the  somatic  and 
germ  cells  to  one  another,  and  to  the  organism  as  a  whole. 

After  very  thorough  study  of  the  chief  types  of  reproduction  through- 
out the  organic  world,  Herbert  Spencer  1  concluded  that  we  are  justified 
in  assuming,  that  every  component  cell  of  the  multicellular  organisms 
has  the  inherent  power,  under  favourable  conditions,  of  developing  into 
the  form  of  the  parental  organism  :  so  that  each  cell  may  be  regarded  as 
potentially  the  whole  organism.  According  to  this  conception — with 
which  Darwin  and  Haeckel  were  in  agreement — the  reproductive  proper-  ^ 
ties  manifested  by  somatic  and  germ  cells  are  the  same  in  kind,  and 
differ  only  in  degree. 

This  doctrine  has  been  strenuously  attacked  by  Weismann  and  his 
followers,  who  have  founded  their  theory  of  heredity  by  continuity  of 
the  germ-plasm,  on  the  assumption  that  the  reproductive  properties  of 
somatic  and  germ-cells  are  specifically  different  :  at  least,  this  was  the 
initial  conception  ;  but,  when  it  was  subsequently  demonstrated  that  in 
many  plants  and  animals  (e.g.,  mosses,  hydra  etc.),  almost  any  cell 
sufficed  for  the  reproduction  of  the  entire  organism,  this  difficulty  was 
met  by  the  supplementary  hypothesis  of  "  accessory "  germ-plasm 
<"  idioplasm  "),  which  in  such  cases  was  supposed  to  have  become  diffused 
throughout  the  soma  protoplasm. 

But  such  a  conception  dispenses  with  the  necessity  for  the  original 
"hypothesis  ;  for,  if  all  or  most  of  the  soma  protoplasm  can  manifest  this 
reproductive  capacity,  it  is  surely  much  more  likely  that  this  property  is 
inherent  in  its  structure,  rather  than  that  it  is  due  to  the  intrusion  of 
hypothetical  "  germ-plasm  "  ab  extra. 

Thus,  in  my  opinion,  the  validity  of  Spencer's  conception  remains 
unimpaired.  As  I  have  fully  set  forth  the  very  convincing  evidence 
supporting  this  conclusion,  in  my  work  on  "  The  Principles  of  Cancer  and 
Tumour  Formation,"2  there  is  no  need  for  me  to  enter  into  detailed 
restatement  of  the  same  here.  For  our  present  purpose;  it  will  suffice  if  I 
recall,  in  the  briefest  manner  possible,  some  of  its  chief  features.  From 
this  standpoint,  what  are  we  to  think  of  the  fact  that  a  single  scale  from 
the  leaf,  stem,  or  root  of  a  plant,  suffices  for  the  reproduction  of  the  whole 
organism  (mosses,  begonia  etc.)  ;  or  that  nearly  as  small  a  particle  of 
the  Hydra  and  other  animals,  is  able  to  reproduce  the  whole  organism  ? 
Does  not  the  whole  history  of  adventitious  gemmation  in  plants,  as 
detailed  in  the  preceding  chapter,  testify  against  fundamental  difference 
between  somatic  and  germ  cells  ?  Is  it  not  the  same  with  gemmation  in 

1  "  Principles  of  Biology,"  1884. 

2  Chap,  xi 


136  THE  NATURAL  HISTORY  OF  CANCER 

animals,  with  asexual  reproduction,  with  metagenesis,  and  with  partheno- 
genesis ?  Do  not  the  phenomena  of  repair,  and  the  reproduction  of  lost 
parts,  testify  to  the  same  effect  ?  I  say  that  they  do. 

The  very  remarkable  manner  in  which  the  majority  of  British 
biologists  were  at  once  captured  by  Weismann's  fascinating  intellectual 
divagation,  is  one  of  the  features  of  the  history  of  the  scientific  life  of  the 
period  :  it  is  likely  to  rank  with  the  celebrated  heresy  of  Liebig,  as  to  the 
non-microbic  nature  of  fermentation,  which  retarded  the  advent  of  the 
microbe  theory  for  such  a  lengthy  period  ;  and  with  the  vagaries  of 
Cuvier,  which  caused  his  curious  hypothesis  as  to  the  origin  of  species,  to 
be  preferred  to  the  more  truthful  conceptions  of  Lamarck,  and  so  retarded 
the  progress  of  modern  biology  for  more  than  half  a  century.  As  the 
veteran  R.  Owen,1  so  well  remarked,  when  these  biological  speculations 
first  began  to  swarm  :  "  If  science  is  to  retain  its  strength,  it  must  keep  in 
touch  with  the  solid  ground  of  observation.  In  reading  some  of  the 
biological  literature  of  the  day,  I  sometimes  rub  my  eyes,  and  wonder 
whether  I  am  not  dreaming  of  the  good  old  days  of  the  Natur-philosophie.'' 
To  be  quite  frank,  I  regard  the  great  body  of  scientific  truth  relating  to 
growth,  reproduction,  variation,  heredity,  and  allied  biological  problems, 
as  being  on  the  whole  more  fully  enshrined  in  the  works  of  Spencer  and 
his  great  lieutenants  Darwin  and  Haeckel,  than  in  any  other  publications  : 
and  it  is  mainly  on  this  basis  that  I  have  built  up  my  doctrine  of  tumour 
formation. 

In  the  genesis  of  tumours,  as  in  the  genesis  of  other  organic  structures, 
I  believe  we  must  take  into  consideration  two  factors — the  cells  whence 
they  originate  and  the  force  that  regulates  the  cellular  activities. 

With  regard  to  the  cells,  although  each  is  largely  dependent  upon 
others,  yet  at  the  same  time  each  manifests  a  certain  independence  or 
autonomy.  In  the  special  changes  underlying  pathological  new  forma- 
tions, the  autonomy  of  the  cells  plays  an  important  part.  It  is  quite 
certain  that  somatic  cells  are  possessed  of  far  greater  reproductive  power, 
than  they  ever  ordinarily  manifest.  Evidence  of  this  is  seen  in  the 
processes  of  repair  and  regeneration,  in  the  changes  that  take  place  at 
puberty  and  in  connexion  with  pregnancy — when  the  breasts  and  uterus 
undergo  such  remarkable  metamorphoses — in  the  phenomena  of  com- 
pensatory hypertrophy,  and  in  a  variety  of  other  processes.  Strange  to 
relate,  this  wonderful  reproductive  capacity,  which  enables  us  to  under- 
stand how  a  single  cell  may  originate  even  the  largest  tumour  extant,  has 
received  but  scant  attention  from  pathologists  in  explaining  the  neoplastic 
process.  That  the  reproductive  activity  actually  manifested  by  somatic 
cells  usually  falls  so  far  short  of  their  potentiality,  is  believed  by  Spencer 
to  be  due  to  the  restraining  and  modifying  influence  exerted  by  the 
whole  organism  on  their  protoplasm  ;  which  is  thus  compelled  to  the 
performance  of  comparatively  subordinate,  modified  functions.  In 
the  performance  of  these  special  duties,  most  of  the  protoplasm  is 
metamorphosed  and  used  up.  Hence,  in  proportion  as  the  cells  are 
highly  specialized,  their  reproductive  function  is  either  greatly  reduced 
or  altogether  lost.  But,  in  the  higher  organisms,  certain  cells  never 
attain  a  high  degree  of  development ;  they  remain  in  a  lowly  organized 
1  Owen's  "  Life,"  vol.  ii.,  p.  330. 


THE  GENESIS  OF  MALIGNANT  TUMOURS  137 

condition,  and  serve — according  as  they  are  more  or  less  unspecialized — • 
either  as  germs  for  reproducing  the  entire  individual,  or  for  forming  and 
maintaining  the  various  tissues  and  organs.  Cells  of  this  kind  abound 
in  all  parts  growing  and  capable  of  growth.  These  are  the  sources 
whence  cancer  and  tumour  germs  are  derived. 

In  the  ordinary  course  of  organic  evolution,  the  processes  of  cell 
growth  and  multiplication  go  on,  until  the  amount  of  structure  proper 
to  the  organism  has  been  produced  ;  then  they  are  restricted  within 
certain  limits.  In  the  healthy  organism,  this  state  of  balanced  equi- 
librium is  maintained  throughout  the  whole  life  of  the  individual.  Herein 
is  evidence  of  a  force  regulating  the  growth  and  development  of  the  tissues 
and  organs  in  relation  to  each  other,  and  to  the  organism  as  a  whole.  In 
order  to  account  for  this,  it  may  be  assumed  that,  by  a  kind  of  selective 
assimilation,  the  molecules  of  each  part  have  the  power  of  moulding  the 
adjacent  nutritive  materials  into  molecules,  after  their  own  kind.  "  Like 
units,"  says  Spencer,  'k  tend  to  segregate,  and  the  pre-existence  of  a 
mass  of  certain  units  produces,  probably  by  polar  attraction,  a  tendency 
for  diffused  units  of  the  same  kind  to  aggregate  with  this  mass,  rather 
than  elsewhere."  In  the  case  of  the  reproduction  of  a  lost  part,  it  must 
be  assumed  that  the  organism,  as  a  wrhole,  exercises  some  such  power 
over  the  newly  forming  part,  so  as  to  make  it  a  repetition  of  its  prede- 
cessor. "  If  a  leg  is  reproduced  where  there  was  a  leg,  and  a  tail  where 
there  was  a  tail,  we  have  no  alternative  but  to  conclude,  that  the  aggregate 
forces  of  the  body  control  the  formative  processes  going  on  in  each 
part."  i 

In  like  manner  the  mimicry — morphological  and  physiological — by 
tumours,  of  the  parts  whence  they  originate,  which  is  always  so  noticeable, 
may  be  explained. 

So  long  as  the  growing  cells  are  subject  to  this  normal  restraining 
influence — which  has  nothing  to  do  with  the  nerves  and  bloodvessels, 
themselves  integrated  structures — :they  develop  in  a  regular  and  orderly 
manner,  in  accordance  with  the  specific  hereditary  tendency  of  the 
whole.  But  when  under  pathological  conditions,  this  restraining 
influence  is  modified  or  withdrawn,  then  their  potential  reproductive 
activity  may  become  actual.  Cells  thus  emancipated  grow  and  multiply 
more  rapidly  than  their  congeners.  This  rejuvenescence  is  the  essence  of 
the  neoplastic  process.  Hyperplasia  and  not  inflammation  is  the  starting- 
point  of  every  neoplasm.  Redundant  agamic  cell  generations  are  thus 
interpolated  in  the  developmental  series,  without  the  concurrence  of  the 
conditions  necessary  for  their  potentialities  attaining  a  physiological 
terminus. 

The  developmental  outcome  of  cells  thus  abnormally  set  free,  depends 
chiefly  upon  the  degree  of  emancipation  attained.  In  plants  and  the  lower 
animals,  such  cells  tend  to  form  new  individuals  by  agamogenesis  ;  but, 
in  the  higher  animals,  the  emancipation  is  never  so  complete,  and  their 
cells  are  always  more  or  less  differentiated  ;  hence,  in  these  organisms, 
instead  of  new  individuals,  only  such  structural  modifications  as  tumours 

1  This  conception  seems  to  me  to  have  far  more  scientific  validity  than  the  alternative 
hypothesis  of  "  tissue  tension,"  etc.,  adopted  by  some  German  pathologists  (Weigert, 
Ribbert,  etc.). 


138  THE  NATURAL  HISTORY  OF  CANCER 

are  produced.  Under  these  circumstances,  wherever  there  is  a  sufficient 
supply  of  nutritive  materials,  capable  of  being  utilized  for  growth  by  the 
cells  of  the  part,  there  a  neoplasm  will  arise  ;  that  is  to  say,  the  abnormally 
emancipated  cells  will  there  grow  and  multiply  more  or  less  independently, 
regardless  to  the  requirements  of  the  adjacent  tissues  and  of  the  organism 
as  a  whole.  In  other  words,  a  new  centre  of  development  has  arisen. 
Thus  the  process  by  which  cancers  and  other  neoplasms  arise  may  be 
regarded  as  a  kind  of  abnormal  gemmation,  the  tumour  being  the  result 
of  the  modified  superinduced  repetition  of  the  developmental  process  ; 
and  its  qualities,  the  result  of  the  degree  of  emancipation  of  its  elements. 
In  the  case  of  malignant  tumours,  cell  potentialities  of  the  highest  order 
have  been  awakened  ;  hence  the  excessive  proliferative  activity  of  their 
constituent  cells  and  their  other  peculiar  features,  which  together 
constitute  malignancy.  / 

If  we  regard  the  cells  combining  to  form  the  higher  animals  as  auto- 
nomous beings,1  possessed  of  morphological  and  physiological  independ- 
ence, we  shall  then  see — although  there  is  no  such  thing  as  true  alterna- 
tion of  generations  in  the  ontogeny  of  such  animals  2 — that,  nevertheless, 
as  Haeckel  has  pointed  out,  a  very  complex  alternation  of  the  constituent 
cells  does  take  place,  which  has  a  resemblance  to  it.  The  developmental 
cycle  commences  with  the  union  of  the  male  and  female  reproductive  cells, 
>vhence  the  cytula  or  fertilized  germ  results  ;  which,  by  agamic  multiplica- 
tion,* originates  the  mass  of  similar  cells  called  the  morula.  These 
differentiate  into  the  various  cells  of  the  blastodermic  layers.  By  further 
agamic  multiplication,  the  cells  of  these  layers  originate  the  very  many 
generations  of  variously  modified  cells,  whence  the  different  tissues  and 
organs  arise.  All  of  these  polymorphic  cell  generations  multiply  agami- 
cally.  Eventually,  however,  two  of  them  differentiate  sexually,  forming 
the  ova  and  sperm  cells.  By  the  union  of  these,  in  the  act  of  sexual 
reproduction,  the  developmental  cycle  is  completed.  The  reversion  of 
the  cells  has  led  them  back  to  their  original  starting-point. 

The  only  difference  between  this  process  and  true  alternation  of 
generation  lies  in  the  fact  that,  in  the  former,  the  products  of  agamo- 
genesis  remain  in  close  contact  with  one  another  to  form  a  multicellular 
organism  ;  whereas,  in  the  latter,  the  agamic  products  (persons),  which 
represent  the  different  generations,  are  separated  and  free.  But,  the 
conditions  prevailing  in  Siphonophora,  show  that  this  distinction  is  not 
of  fundamental  importance  ;  for,  in  these  creatures,  the  same  persons — 
widely  differentiated  by  division  of  labour — remain  united  into  one  stock, 
that  in  the  other  hydro-medusae  lead  separate  and  independent  lives. 
Thus,  when  the  phenomena  of  gemmation  and  pathological  neoplasia  are 
examined  in  this  light,  it  is  obvious  that  the  essential  thing  in  both  cases, 
is  the  interpolation  in  the  developmental  series  of  additional  agamic  cell 

"  All  the  facts  at  our  command  indicate  that  the  tissue-cells  possess  the  same 
morphological  organization  as  the  egg-cell  or  the  protozoon  ;  and  the  same  fundamental 
physiological  properties  as  well,"  says  E.  B.  Wilson,  the  ablest  exponent  of  cellular 
biology  for  English-speaking  peoples  (1903). 

2  According  to  Pr.  Beard,  even  in  mammalia  true  alternation  of  generations  does  occur, 
the  asexual  larva  being  represented  by  the  chorion  ;  but,  at  present,  this  speculation  is  no 
more  than  an  unproved  hypothesis.  The  conception,  however,  is  of  interest ;  and,  ou 
general  a  priori  grounds,  there  is  much  in  its  favour. 


THE  GENESIS  OF  MALIGNANT  TUMOURS  139 

generations,  owing  to  the  excess  of  nutrition  in  these  situations.  From 
this  standpoint,  tumour  formation  appears  as  a  reversion  from  dominant 
gamogenesis,  to  a  form  of  agamogenesis. 

It  follows  from  the  foregoing,  that  the  genesis  of  cancer  and  other 
tumours,  is  a  phenomenon  of  the  same  order  as  discontinuous  growth  in 
general. 

Just  as  cells  embedded  in  the  stroma  of  an  ovarium,  become  ova  by 
excessive  growth,  at  the  expense  of  adjacent  nutritive  materials,  which 
they  divert  from  other  cells  ;  so  we  may  infer  that  those  cells  which 
originate  tumours,  become  different  from  their  congeners  in  a  similar  way. 


Tumour   Formation   and    Developmental    Irregularity,    with   Special 
Reference  to  the  Role  of  "  Rests  "  in  the  Origin  of  Tumours. 

I  have  previously  referred  to  tumour  formation,  as  being  the  outcome 
of  a  futile  attempt  of  certain  cells  to  repeat  agamic  ally  a  greater  or  less 
portion  of  the  ontogenesis. 

In  order  to  elucidate  the  various  types  of  tumours  and  their  diverse 
qualities  from  this  standpoint,  it  is  necessary  to  pay  particular  attention 
to  the  germs  whence  they  originate  ;  and  to  the  time  at  which  the  process 
starts. 

Cohnheim,  who  was  the  first  to  study  this  question  systematically, 
thought  that  the  germs  of  all  tumours  were  fragments  of  the  fertilized 
germinal  matrix,  sequestrated  during  the  earliest  period  of  embryonic 
life.  His  tumour  germs  were  therefore  blastogenic.1 

The  researches  of  embryologists  and  teratologists,  have  shown  that 
tumour  germs  of  this  kind  may  really  exist. 

Having  destroyed  one  of  the  first  two  cells  resulting  from  the  initial 
division  of  the  impregnated  frog's  egg,  Roux,  Hertwig,  Chabry  and 
Morgan,  found  that  the  other  cell,  nevertheless,  developed  into  a  whole 
embryo  of  half  the  normal  size  ;  by  shaking  the  germs  of  various  animals 
and  so  separating  the  blastomeres,  Driesch,  Wilson  and  others  found, 
that  each  detached  blastomere  likewise  developed  into  a  whole  embryo 
of  half-size.  It  has  been  found  that  blastomeres  isolated  at  even  the 
four-,  eight-,  or  sixteen-cell  stages,  may  sometimes  develop  into  small 
but  complete  embryos.  At  later  stages,  however,  detached  cells  are  never 
capable  of  undergoing  such  complete  developmental  exegesis  ;  for,  as 
Driesch  and  others  have  shown,  when  pieces  are  cut  from  the  evolving 
organism  after  gastrulation,  they  do  not  develop  into  perfect  larvae,  but 
only  into  various  defective  or  monstrous  forms.  These  experiments 
indicate  that  the  power  of  a  single  cell  to  reproduce  the  entire  organism 
is,  in  the  highest  animals,  limited  to  the  earliest  stages  of  cleavage  ;  for 
it  is  only  these  cells  that  contain  all  the  elements  requisite  for  complete 
developmental  exegesis. 

In  the  course  of  his  various  experiments,  Roux  often  noticed  in  frog 
embryos  with  closed  medullary  canal,  isolated  blastomeres,  belonging  to  a 

1  Even  before  Cohnheim's  time,  Liicke  and  others  had  advocated  a  similar  origin  for 
teratomata. 


140  THE  NATURAL  HISTORY  OF  CANCER 

much  earlier  developmental  stage  ;  *  and  these  he  thought  might  become 
tumour  germs.  Beard  has  met  with  a  similar  condition  in  studying  the 
embryology  of  Raja  batis ;  while  Barfurth,  experimenting  as  to  the 
regeneration  of  the  germinal  layers,  found  when  these  were  punctured  in 
-xC  the  gastrula  stage,  so  that  cells  were  displaced  and  involuted,  that  these 
heterotopic  elements  nevertheless  continued  their  growth,  in  such  a 
manner  as  suggested  the  probability  of  their  eventually  becoming  tumour 
germs. 

Wilson,  Roux,  and  others,  by  shaking  and  various  other  mechanical 
devices  tending  to  separate  the  blastomeres,  found  that  in  this  way 
homologous  twins  and  various  grades  of  double  mounters  were  frequently 
produced. 

By  the  implantation  of  blastoderms  of  fowl's  eggs,  embryos,  and 
fragments  of  the  same,  into  the  subcutaneous  tissues  of  chicks,  Fere  2 
claims  to  have  succeeded  in  producing  teratomatous  tumours  artificially  ; 
and  the  remarkable  result  obtained  by  Nichols,3  by  implanting  the  entire 
foetus  into  the  subcutaneous  tissue  of  the  mother,  whence  ajbumour — very 
like  a  teratoid — was  produced,  supports  Fere's  claims. 

It  follows  from  consideration  of  the  foregoing  facts,  that  the  only  kind 
of  tumours  likely  to  arise  from  Cohnheim's  blastogenic  germs,  are  those  in 
which  the  whole  ontogenetical  cycle  is  structurally  represented ;  that  is 
to  say,  the  embryomata  or  teratoid  tumours,  which  may  be  regarded  as 
the  very  imperfect  twin  brothers  or  sisters  of  the  porteur.  This  kind  of 
neoplasm  is  the  type  of  tumour  formation  in  excelsis.  Such  tumours 
might  with  equal  propriety  be  classed  with  the  double  monsters  by 
inclusion,  for  they  are  identical  with  those  formations  described  by 
teratologists  as  foetus  in  fcetu.  So  far  then  as  these  tumours  are  con- 
cerned, tumour  genesis  is  seen  to  be  akin  to  teratogenesis — developmental 
irregularity  being  the  factor  common  to  both. 

It  seen?!  not  unreasonable  to  regard  the  process  by  which  such  results 
are  attained,  as  being  a  kind  of  reproduction  by  gemmation  ;  here,  as  in 
the  lowest  organisms,  when  the  growth  of  the  fertilized  germ  exceeds  a 
certain  amount,  it  tends  to  the  formation  of  one  or  more  new  individuals, 
rather  than  to  further  enlargement  of  the  original  one. 

Cohnheim  thought  that  his  blastogenic  tumour  germs  might  begin 
their  growth  into  tumours  immediately  after  sequestration,  or  at  any 
subsequent  period  of  the  ontogenesis  ;  or  that  they  might  lie  dormant  in 
the  tissues,  without  ever  undergoing  any  further  change.  The  life- 
history  of  teratoid  tumours  seems  to  warrant  this  suggestion  ;  which  is 
also  in  accordance  with  appearances  observed  by  embryologists. 

It  not  unfrequently  happens  that  malignant  neoplastic  changes — 
epitheliomatous  and  sarcomatous — supervene  in  connexion  with  these 
teratoid  formations  ;  and  changes  of  this  kind  are  no  doubt  of  commoner 
occurrence  in  them,  than  in  the  corresponding  parts  of  normally  con- 
stituted beings.  This  is  only  what  might  be  expected  a  priori,  considering 


1  R.  Owen  was  one  of  the  first  biologists  who  specially  called  attention  to  aberrant 
lin  unchanged  and  become  included  in  the  body  of 


cells  of  this  kind  :  "  which  may  remain 
the  embryo  "  ("Parthenogenesis,"  1849). 

2  C.  R.  Soc.  de  Biologie,  1905  ;  also  Arch.  d'Anat.  Micros.,  1897-1898. 

3  Third  Report  Croft  Cancer  Committee  of  Harvard  Medical  School,  1905,  p.  120. 


THE  GENESIS  OF  MALIGNANT  TUMOURS  141 

the  manifold  imperfections  in  their  development,  and  especially  their 
undue  richness  in  lowly  organized  cells  still  capable  of  growth  and 
development ;  and,  therefore,  endowed  with  a  high  degree  of  proliferative 
potentiality. 

From  the  genet ical  standpoint,  tumours  may  with  propriety  be 
divided  into  two  classes  :  (a)  the  teratoid  (blastogenic)  ;  and  (6)  the 
histioid  (somatogenic). 

It  is  to  the  genesis  of  the  latter  group  of  tumours,  that  we  now  have 
to  direct  our  attention. 

As  I  have  previously  remarked,  after  gastrulation  and  the  differentia- 
tion of  the  germinal  layers,  no  cells  are  ever  formed  in  the  higher  animals, 
like  those  of  the  morula,  whence  a  complete  new  being  may  be  formed. 
Cells  subsequently  arising  can  only  develop  certain  tissue  structures, 
viz.,  those  which  are  normally  derived  from  the  germinal  layer  whence 
they  originate  ;  thus,  derivatives  of  the  epiblast  always  remain  within 
this  type,  and  never  originate  mesoblastic  structures,  and  vice  versd.  In 
the  development  of  tumours,  the  same  law  is  observed  :  there  are  among 
these  formations  no  transitions  from  one  tissue-type  to  another.  It  is  * 
necessary  to  insist  on  this,  because  some  modern  pathologists  still  uphold  A  ; 
the  ancient  doctrine  of  metaplasia — countenanced  by  Virchow — according 
to  which,  the  connective  tissue  is  regarded  as  an  indifferent  matrix, 
whence  any  tissue  may  arise.  This  doctrine  ignores  the  specificity  of 
the  tissue  elements,  which  embryology  has  revealed  ;  and  it  must  therefore 
be  rejected. 

From  the  foregoing  considerations,  it  follows  that  the  physiological 
prototype  of  a  histioid  tumour,  must  be  something  less  than  an  entire 
individual :  their  prototypes  are,  in  fact,  to  be  found  in  the  various  organs 
and  tissues  of  the  body,  as  they  are  formed  after  the  differentiation  of  the 
germinal  layers,  whether  in  pre-  or  post-natal  life.  Thus,  the  precise 
period  of  time  at  which  histioid  tumours  may  originate  is  subject  to  wide 
variation,  and  this  entails  in  the  resulting  neoplasms  corresponding 
diversities  ;  for,  as  ontogenesis  proceeds,  there  is  concomitant  differentia- 
tion, first  of  the  cytoplasm  of  the  cells  and  subsequently  of  their  nuclei, 
whereby  progressive  loss  of  reproductive  capacity  is  entailed,  so  that — 
in  certain  cells — it  may  eventually  be  impossible  to  elicit  any  proliferative 
activity  by  ordinary  stimuli. 

Hence  the  portion  of  the  ontogenetical  cycle  mimicked  by  histioid 
tumours,  must  necessarily  in  all  cases  be  less  than  that  compassed  by 
their  teratoid  congeners  ;  but,  between  these  extremes,  all  grades  of 
intermediate  variations  occur. 

In  the  ordinary  course  of  organic  evolution,  the  grqwth  and  develop- 
ment of  the  cells  proceeds  in  a  regular  and  ordinary  manner,  in  accordance 
with  the  specific  hereditary  tendency  of  the  whole.  But  the  process  once 
started,  does  not  cease  on  account  of  irregularity,  or  because  it  is  taking  a 
wrong  direction.  Hence  cells  may  arise  at  a  place  where  they  have  no 
business  ;  or  at  a  time  when  they  ought  not  to  be  produced  ;  or  to  an 
extent  that  is  at  variance  with  the  normal  formation  of  the  organism. 

In  the  earliest  stages  of  ontogenesis,  as  we  have  seen,  teratoid  tumours 
and  double  monsters  are  among  the  consequences  of  these  developmental 


142  THE  NATURAL  HISTORY  OF  CANCER 

irregularities  ;  and,  at  later  periods,  the  various  histioid  tumours,  in  like 
manner  result. 

The  rudiment  of  the  embryo  begins  to  appear  very  soon  after  gastrula- 
tion  ;  and  by  the  end  of  the  third  month  of  intra-uterine  life,  the  general 
form  of  the  body  and  its  members  is  well  denned.  The  germs  of  the 
more  complicated  forms  of  "  mixed  tumour,"  dermoids,  etc.,  are  probably 
caused  by  developmental  disturbances  affecting  the  embryo,  during  the 
earlier  part  of  this  period.  As  the  life-history  of  these  formations  shows, 
malignant  neoplastic  disease  may  originate  from  them  at  any  stage  of 
their  exegesis  ;  and  there  a^e  good  reasons  for  believing  that  they  are  more 
prone  to  originate  such  changes,  than  are  their  normally  evolved  tissue 
prototypes. 

Later  developmental  disturbances,  which  may  even  extend  to  the 
post-natal  period,  cause  less  extensive  reactions  ;  confined,  for  instance, 
to  the  rudiments  of  particular  organs,  parts  or  to  single  tissues  etc. 

Underlying  the  above  remarks  is  the  assumption,  that  the  germs  of 
histioid  tumours  arise,  like  those  of  teratoid  tumours,  by  sequestration 
of  fragments  of  the  matrix  of  the  evolving  organs,  tissues  etc.,  at  different 
stages  of  their  exegesis,  owing  to  various  forms  of  more  or  less  local 
developmental  irregularity. 

For  the  moment,  let  us  assume  that  all  histioid  tumours  arise  from 
germs  of  this  kind,  which  we  will  call  "  rests."  Of  these  structures,  as 
of  their  blastogenic  congeners,  it  may  be  predicated  from  study  of  the 
life-history  of  histioid  tumours  ;  that  they  may  begin  to  grow  into 
tumours  forthwith,  or  at  any  subsequent  period  of  the  developmental 
stage,  or  that  they  may  remain  permanently  latent  in  the  tissues. 

In  order  to  further  elucidate  the  role  of  "  rests  "  in  the  origin  of 
histioid  tumours,  it  will  be  well  to  review  the  evidence  bearing  on  this 
subject,  that  has  accumulated  of  late  ;  especially  as,  in  the  publications 
of  British  pathologists,  this  subject  has  hitherto  been  very  inadequately 
treated. 

When  this  theory  of  tumour  genesis  was  first  announced,  very  few 
facts  could  be  adduced  in  support  of  it.  No  one  then  believed  in  the 
possibility  of  such  an  amount  of  developmental  irregularity  as  it  pre- 
supposed. The  light  of  modern  science  has,  however,  effectually  dissi- 
pated this  misconception  ;  and  our  eyes  have  been  opened  to  the  hidden 
defects  of  normality.  Sequestrated  fragments  of  the  various  tissues  and 
organs  have  now  been  found  to  exist,  in  every  part  of  the  body  that  has 
been  specially  examined  for  them.  In  short,  it  is  evident  that,  in  the 
course  of  ontogeny,  innumerable  fragments  of  the  evolving  tissues  and 
organs  are  thrown  off  ;  which,  as  development  proceeds,  become  embedded 
in  the  tissues — whe-e,  as  a  rule,  they  remain  quiescent.  Thus,  during 
the  last  thirty  years,  pathologists  have  added  a  new  chapter  to  human 
morphology  ;  of  which,  however,  the  anatomists — as  yet — seem  hardly 
to  be  aware.  It  is  to  belated  structures  of  this  kind,  that  the  term 
"  rests  "  is  applied.  My  conception  of  the  significance  of  this  term 
differs  somewhat  from  Cohnheim's.  He  thought  that  "  rests  "  consisted 
solely  of  germ  elements  ;  which,  after  sequestration,  lay  dormant  in  the 
body  as  embryonic  rudiments.  As  previously  mentioned,  "  rests  "  of 


THE  GENESIS  OF  MALIGNANT  TUMOURS  143 

this  kind  probably  exist,  and  from  them  blastogenic  tumours  arise  ;  but, 
the  "  rests "  with  which  histology  has  made  us  acquainted,  always 
present  indications  of  having  undergone  more  or  less  developmental 
exegesis,  along  the  lines  proper  to  the  parental  tissue. 

Long  before  Cohnheim's  time,  the  proneness  of  certain  congenital 
defects  to  originate  malignant  tumours  had  been  recognized  by  patho- 
logists,  especially  by  Paget,  Pemberton,  and  Virchow.  That  naevi  are 
particularly  apt  to  develop  malignant  disease,  is  a  very  ancient  dis- 
covery ;  it  was,  for  instance,  well  known  and  commented  on  by  Recamier, 
Walther  and  others,  at  the  beginning  of  the  nineteenth  century.  Even 
as  far  back  as  1853,  referring  to  the  proneness  of  melanomata  to  arise 
from  pigmented  moles,  Paget  x  said  :  "  It  seems  a  striking  illustration  of 
the  weakness  in  resisting  disease,  which  belongs  to  parts  congenitally 
abnormal."  In  another  passage  he  adds  :  "  This  peculiarity  may  make 
us  suspect  that  there  may  be  other,  though  invisible,  defects  of  first 
formation  in  our  organs,  which  may  render  them,  or  even  small  portions 
of  them,  peculiarly  apt  for  the  seats  of  malignant  and  other  specific 
diseases." 

In  1858,  Pemberton2  pointed  out  that  of  thirty-four  cutaneous 
melanomata,  studied  by  him,  no  less  than  fifteen  obviously  arose  from 
congenital  nsevj.  moles,  warts,  or  other  local  blemishes. 

About  the  period  1854-1855,  Remak  3  having  demonstrated  the  origin 
of  "  cholesteatomata "  from  detached,  invaginated,  epidermoidal 
"  rests "  ;  also  showed  that  the  occurrence  of  malignant  epithelial 
tumours,  in  regions  where  epithelium  is  normally  non-existent,  was  the 
result  of  heterotopia  of  pre-natal  origin. 

Roser,4  at  about  the  same  time,  traced  the  origin  of  dermoids  of  the 
neck  to  sequestration  of  epidermoidal  elements,  in  connexion  with  the 
closure  of  the  branchial  clefts  ;  while  Verneuil 5  demonstrated,  in  a  very 
conclusive  manner,  the  genetic  connexion  between  scrotal,  testicular 
and  other  dermoids,  and  somewhat  similar  local  developmental 
irregularities. 

Subsequently  Virchow  6  developed  the  subject  still  more  fully,  showing 
that  sarcomatous  tumours  of  the  skin  often  originated  from  ngevi,  moles, 
soft  warts  (verrucas  molles),  and  other  congenital  anomalies. 

Under  these  circumstances,  it  seems  unreasonable  for  the  admirers  of 
Durante 7  to  claim  for  him  the  authorship  of  the  "  rest  "  theory  of 
tumours,  because  he  published — a  year  or  two  before  Cohnheim's  "  Vor- 
lesungen  "  appeared — a  brochure  8  on  :  "  The  Physico-pathological  Con- 
nexion between  Maternal  Nsevi  and  the  Genesis  of  some  Malignant 
Tumours.v  Paget  and  Virchow  never  advanced  such  claims,  although 
they  were  far  more  entitled  to  do  so  than  Durante.  The  truth  is,  for 

Surgical  Pathology,"  1853,  vol.  S.,  p.  490. 

Observations  on  Pathology,  etc.,   of  Cancerous   Diseases,"   part  i.  (Melanosis), 
185  . 

Deutsche  Klinik,"  1854,  p.  160. 
Handb.  d.  Anat.-chir.,"  1854. 

Mem.  sur.  1'inclusion  scrotale  et  testiculaire,"  1855. 
Path,  des  Tumeurs,"  1869,  t.  ii.,  p.  218  et  seq. 
Eyre,  British  Medical  Journal,  1896,  vol.  ii.,  p.  1441. 
Archiv.  di  Palasciano,  May,  1874. 


144  THE  NATURAL  HISTORY  OF  CANCER 

those  acquainted  with  the  works  of  Paget  and  Virchow,  there  was  nothing 
new  in  Durante's  publication.  The  credit  of  elaborating  the  indications 
furnished  by  these  pioneers,  together  with  his  own  observations,  into  a 
comprehensive  theory  of  tumours,  and  making  the  same  known  to  the 
profession  in  general,  undoubtedly  belongs  to  Cohnheim.  This  concep- 
tion seems  to  have  originated  in  his  mind,  through  careful  study  of  a  case 
of  renal  myo-sarcoma  that  came  under  his  observation,  in  an  infant 
sixteen  months  old.  The  left  lumbar  region  was  occupied  by  a  large  cir- 
cumscribed tumour,  which  had  destroyed  most  of  the  Sidney  by  com- 
pression, the  remains  of  this  organ — otherwise  unaltered — being  adherent 
to  it.  Within  the  capsule  of  the  right  kidney — at  its  upper  end — there 
was  also  a  similar  rounded  tumour,  quite  distinct  from  the  renal  substance. 
Both  tumours  were  sarcomatous,  and  comprised  in  their  structure  striped 
muscle  elements.  It  seemed  evident  to  him,  that  tumours  thus  circum- 
stanced could  only  have  arisen  from  heterotopic  elements,  detached  from 
their  normal  connexions  during  early  pre-natal  life  ;  hence,  other  facts 
known  to  him  concurring,  he  concluded  that  all  tumours  thus  originated. 


Uterine  Tumours  and  "  Rests." 

We  have  now  to  study  a  little  more  closely  the  genesis  of  histioid 
tumours  from  "  rests  "  ;  and,  as  this  is  far  too  large  a  subject  to  treat  here 
in  detail,  I  must  be  satisfied  with  giving  a  few  typical  examples.  For 
this  purpose,  I  have  selected  uterine  and  mammary  tumours,  as  I  have 
made  a  special  study  of  these  ;  another  reason  for  so  doing  being,  that 
tumours  of  these  organs  have  hitherto  received  hardly  any  attention  in 
this  connexion. 

Myoma. — By  far  the  commonest  non-malignant  tumour  to  which 
humanity  is  prone  is  the  familiar,  but  little  studied,  uterine  ''  fibroid,"  or 
myoma,  whose  structure  so  closely  resembles  that  of  the  uterine  muscu- 
lature, as  to  suggest  the  probability  of  these  tumours  being  little  more 
than  overgrown  fragments  thereof,  which  thorough  study  of  the  ensemble 
of  the  subject  emphatically  confirms.  Moreover,  it  will  be  proved  that 
the  germs  whence  these  tumours  arise  are  sequestrated  during  pre- 
natal life.  The  great  frequency  with  which  uterine  myomata  are  multiple, 
might  of  itself  lead  us  to  suspect  the  association  of  developmental  irregu- 
larity with  the  origin  of  these  tumours  ;  while  the  occurrence  of  cases  in 
which  the  whole  musculature  is  replaced  by  dense  masses  of  small  tumours 
— to  which  I  shall  subsequently  have  to  refer  more  in  detail — specially 
points  to  this  conclusion. 

Although  the  germs  whence  most  myomata  arise  are  of  pre-natal  origin, 
it  is  rare — as  in  the  case  of  such  obviously  congenital  tumours  as  teratoids 
and  dermoids — to  meet  with  tumours  of  this  kind  during  early  life  : 
Pick  !  has,  however,  described  two  cases  of  congenital  myoma,  in  each  of 
wrhich  the  nascent  tumour  seemed  to  have  caused  uterine  duplicity,  by 
interfering  with  the  blending  of  the  lower  segments  of  the  Miillerian 
ducts  ;  and,  in  a  case  reported  by  Landau,2  a  myomatous  tumour — 

1  Monats.  f.  Oeb.  u.  Gyn.,  October,  1897. 

2  Berlin,  klin.   Woch.,  No.  8,  1901. 


THE  GENESIS  OF  MALIGNANT  TUMOURS  145 

obviously  of  congenital  origin — occupied  the  place  of  the  cervix  uteri, 
and  by  compressing  the  Miillerian  ducts  in  the  pre-natal  period  had  caused 
atresia  uteri,  there  being  no  canalis  cervicalis  :  this  tumour  contained 
numerous  epithelial  inclusions,  which  appeared  to  be  Wolffian  residua. 

The  fact  that  uterine  myomata  often  contain  various  heterotopic 
inclusions — comprising  epithelial,  cartilaginous,  calcareous,  osseous, 
mucoid,  fatty  and  even  rhabdomyomatous  elements — points  to  their 
pre-natal  origin. 

Recent  researches  (Rosger,  Kleinwachter,  Sobotta  etc.)  have  shown 
that  the  development  of  the  uterine  musculature,  is  closely  associated  X 
with  that  of  its  numerous  bloodvessels.  The  nascent  utero-vaginal 
canal,  having  no  proper  musculature  of  its  own,  is  provided  with  the  same 
through  the  agency  of  a  matrix  of  mesoblastic  cells,  which  creep  round  it 
with  the  evolving  bloodvessels.  Should  (he  development  of  the  latter 
be  arrested,  when  this  process  has  already  made  some  progress,  the  out- 
come might  well  be  just  such  fragmentation  of  the  musculature,  with 
more  or  less  overgrowth  of  the  fragments,  as  in  the  specimens  described 
in  the  following  case  records,  which  seem  to  be  quite  unknown  to  con- 
temporary gynaecologists  : — 

1.  This  patient  was  under  the  care  of  Emmet.1     When  first  seen  by 
him  she  was  in  a  very  weak  and  emaciated  condition.     There  was  great 
abdominal  distension  from  the  tumour,  and  she  suffered  much  from 
pressure  symptoms.     Strange  to  say,  there  was  no  metrorrhagia.     She 
died  of  exhaustion  soon  after  Emmet  first  saw  her. 

At  the  necropsy,  the  tumour  was  found  to  consist  of  the  greatly 
enlarged  uterus,  converted  into  a  large  conglomerate  of  hundreds  of 
myomatous  nodules — none  of  great  size — held  together  by  a  thin  over- 
lying capsule,  through  which  their  inequalities  could  be  seen  and  felt.  On 
section  the  mass  presented  the  appearance  shown  in  Fig.  6  (next  page).  The 
division  was  made  with  difficulty,  as  many  of  the  tumours  were  of  dense 
fibrous  nature,  and  others  were  calcified.  The  bloodvessels  of  the  part 
were  obliterated  to  such  an  extent,  that  only  the  peripheral  nodules  pre- 
sented any  signs  of  vascularity.  Emmet  subsequently  met  with  a  second 
case  of  the  same  kind. 

2.  Meadows  2  has  described  a  similar  case  as  follows  :  "  I  have  seen 
the  uterus  completely  studded  with  myomata,  both  within  and  without, 
so  that  on  making  a  section  of  the  uterine  wall,  the  surface  looked  like 
the  skin  of  a  person  with  small-pox  ;  so  numerous  were  the  tumours  that 
it  was  impossible  to  count  them.     They  varied  in  size  from  a  millet-seed 
or  less,  to  that  of  a  small  walnut." 

3.  Cruveilhier  3  has  encountered  the  like  condition.     In  his  case  the 
whole  musculature  was  replaced  by  a  multitude  of  small  tumours  of  this 
kind,  most  of  which  were  very  minute,  the  largest  being  no  bigger  than  a 
walnut.     Many  of  the  tumours  were  calcified.     The  affected  uterus  pre- 
sented as  an  irregularly  bossed  mass,  not  unlike  an  ovarian  cystoma  to 
look  at.     Some  of  the  tumours  projected  externally  and  others  internally, 
but  most  of  them  were  embedded  in  the  musculature. 


_., gj,  1880,  p.  525.  2  Gynaecology . 

3  "  Anatomic  Pathologique,"  t.  ii.,  liv.  xxiv.,  p.  6. 

10 


146  THE  NATURAL  HISTORY  OF  CANCER 

Bland-Sutton *  and  Haultain 2  have  also  met  with  this  condition, 
which  each  of  them  regarded  as  "  unique,"  being  unaware  of  the  very 
explicit  account  of  this  malady  in  my  book  on  "  Uterine  Tumours." 

Instead  of  involving  the  whole  organ,  multiple  myomata  are  sometimes 
limited  to  a  special  part.  In  the  Hunterian  Museum,3  is  a  uterus  with 
numerous  tumours  of  this  kind,  which  occupy  every  part  of  it,  except  the 
cervix  and  portio,  which  are  free.  Rabenau  4  has  met  with  similar  tumours 
limited  to  the  cervix  and  portio.  Stone  5  has  described  a  multinodular 
tumour  of  the  corpus,  which  consisted  of  an  immense  number  of  small 
growths  of  vsfcrious  shapes. 

If  we  conceive  this  process,  as  restricted  to  a  still  narrower  area — to  a 


FIG.  6. — MULTIPLE  MYOMATA  INVOLVING  THE  WHOLE  UTEEDS  (EMMET). 
The  white  areas  represent  calcified  tumours. 

few  vascular  branches,  or  even  to  a  single  one — it  is  easy  to  understand 
how  the  germs  of  ordinary  myomata  arise.  Thus,  these  cases  are  of 
great  importance,  for  enabling  us  to  understand  the  pathogenesis  of 
myomata. 

In  some  instances,  these  abnormally  evolving  myomatous  elements 
are  intimately  connected  with  "  rests  "  of  Wolffian  or  Miillerian  struc- 
tures, or  even  of  the  uterine  mucosa  itself.  The  discovery  of  epithelial 
inclusions  in  uterine  myomata,  was  one  of  the  earliest  indications  of  the 

1  British  Medical  Journal,  1901,  vol.  i.,  p.  814. 

2  Transactions  of  the  Edinburgh  Obstetrical  Society,  1905,  vol.  xxx.,  p.  112. 

3  No.  4,627,  Pathological  Series. 

4  Berlin,  klin.  Woch.,  1882,  vol.  xix.,  p.  170. 

5  American  Journal  of  Obstetrics,  etc.,  October,  1899,  p.  519. 


THE  GENESIS  OF  MALIGNANT  TUMOURS  147 

correctness  of  this  interpretation.  The  presence  of  these  foreign  elements 
was  first  demonstrated  by  Babes,1  and  Diesterweg,2  in  1882  ;  and  their 
observations  have  since  been  confirmed  and  amplified  by  Shottlander, 
Hauser,  Ricker,  Orloff,  Recklinghausen,  Meyer,  Hirst,  and  others.  They 
present  either  as  solid  cellular  aggregations  of  various  shapes  and  sizes,  or 
as  tubules,  cysts,  or  structures  not  unlike  utricular  glands ;  in  any  case, 
the  peripheral  cells  are  of  more  or  less  columnar  or  cubical  shape,  and 
they  may  be  ciliated.  Many  observers  (Meyer,  Tourneux,  Ricker,  Fischel, 
Coblenz  etc.)  have  found  similar  epithelial  inclusions — from  which  they 
believe  certain  cysts  arise — in  the  otherwise  normal  uterine  musculature. 

By  Babes  and  Recklinghausen  these  structures  are  believed  to  be 
Wolffian  relics,  while  other  pathologists  insist  on  their  Miillerian  origin. 
But  all  such  bodies  are  not  necessarily  either  Wolffian  or  Miillerian 
residua,3  for  they  may  be  included  sequestra  from  the  uterine  mucosa 
itself.  Indeed,  Ribbert  has  found — deep  in  the  uterine  wall — not  only 
sequestrated  utricular  glands,  but  even  isolated  fragments  of  the  entire 
mucosa.  In  this  connexion  it  is  worth  noting  that,  according  to 
R.  Meyer,4  glandular  structures  are  found  in  the  mucosa,  even  as  early  as 
the  seventh  month  of  foetal  life,  and  they  often  penetrated  deeply  and 
were  even  aberrant ;  but  this  pre-natal  origin  for  the  uterine  mucosal 
glands  is,  of  course,  contrary  to  the  usually  received  opinion,  according 
to  which  these  structures  are  entirely  of  post-natal  origin.  In  the  face  of 
Meyer's  results,  however,  this  opinion  can  no  longer  be  maintained. 

Heterotopic  epithelial  elements,  are  not  present  in  all  myomata,  and 
the  exact  proportion  of  cases  in  which  they  occur  has  yet  to  be  deter- 
mined ;  the  careful  researches  of  Orloff,  who  examined  serial  sections  of 
fifty-five  specimens  of  small  myomata,  revealed  only  four  instances  of 
epithelial  inclusions. 

The  researches  of  Coblenz,  Meyer,  Recklinghausen  and  others,  have 
shown  that  the  track  of  the  utero- vaginal  canal  is  strewn  with  epithelial 
debris,  chiefly  of  Wolffian  origin  ;  hence,  it  is  not  surprising,  in  the  process 
of  building  up  the  musculature,  and  in  the  coming  together  of  the  various 
ducts  from  the  fusion  of  which  the  uterus  and  vagina  result,  that  these 
aberrant  epithelial  elements  are  sometimes  included  in  myomatous 
sequestrations  ;  and  no  doubt  the  migrations  and  changed  relations  of 
the  parts  incidental  to  ontogeny,  as  well  as  the  correlations  between  the 
musculature  and  its  numerous  bloodvessels,  which  are  so  extraordinarily 
interwoven,  are  also  favouring  factors.  Such  is  the  manner  in  which  I 
believe  the  germs  of  myomata  originate. 

Some  of  those  who  have  specially  studied  the  subject,  believe  that 
germs  of  this  kind  also  arise,  by  a  similar  process,  during  post-natal  life  ; 
but,  if  this  really  be  so,  it  has  yet  to  be  proved.  So  far  as  I  can  judge, 
the  general  drift  of  the  ensemble  of  the  evidence  now  available,  is  decidedly 

1  Allgem.  Wien.  med.  Zeitung,  1882,  Nos.  36  and  48. 

2  Zeits.  f.  Oeb.  u.  Gyn.,  1883,  vol.  ix.,  p.  191. 

3  Evelt   (Munch,   med.    Woch.,  August   18,    1903)   having  reported   an  instance   of 
melanotic  malignant  tumour,  as  primarily  arising  from  a  corpus  myoma,  this  raises  the 
question  of  ectodermal  inclusions  in  such  tumours ;  and,  on  the  hypothesis  of  ectodermal 
"  rests,"  other  instances  of  primary  uterine  melanoma  may  thus  be  accounted  for. 

*  "  Ueber  epitheliale  Gebilde  im  Myometrium  des  f  cetalen  und  kindlichen  Uterus  "  etc. 
Berlin,  1902. 

10—2 


148  THE  NATURAL  HISTORY  OF  CANCER 

^-  against  this  hypothesis  :  the  germs  of  myomata  always  appear  to  be  of 
/  pre-natal  origin. 

In  this  connexion  it  is  well  to  remember,  thafc  myomata  are  not 
confined  to  the  uterus  and  its  vicinity,  although  they  are  of  much  more 
frequent  occurrence  here  than  elsewhere.  Like  their  uterine  congeners, 
the  extra-uterine  myomata  are  often  multiple  ;  and  they  not  infrequently 
contain  epithelial — and  more  rarely  other — inclusions. 

If  the  foregoing  views  as  to  the  origin  of  myomata  be  correct,  it  follows 
that  extrinsic  factors,  such  as  local  irritation  and  chronic  inflammation — 
whether  due  to  traumata,  microbes,  or  other  external  irritants — play 
but  a  secondary  part  in  their  causation. 

In  concluding  this  subject,  I  have  only  to  remark  that  malignant 
disease  sometimes — but  rarely — originates  from  myomatous  tumours  ; 
but  of  this  more  anon. 

Lipoma. — Although  fatty  tissue  is  not  normally  present  in  the  uterus, 
yet,  as  I  have  before  mentioned,  it  is  sometimes  found  included  in  myo- 
mata (T.  Smith,  Jacobson,  Briinings,  Seydel)  ;  moreover,  instances  of 
fatty  tumours  in  the  uterus  have  been  reported  (Knox,  Stroinski,  Busch, 
Orth,  A.  G.  Ellis,  Merkel  [two  cases],  and  Seeger).  The  only  rational 
explanation  of  these  heterotopic  formations  is  sequestration,  with  dis- 
placement of  fatty  tissue  matrix  during  the  pre-natal  period.  Fatty 
tumours  have  also  been  found  in  the  vicinity  of  the  uterus — e.g.,  in  the 
broad  ligaments  (Treves,  Prenice,  Terrilon),  round  ligaments  (Witte), 
recto-vaginal  septum  (S.  Wells,  Pelletan),  tube  (Parona),  recto-uterine 
cul-de-sac  (Laffore)  etc.  ;  where  they  are  just  as  heterotopic  as  in  the 
uterus  itself. 

Osteoma  and  Chondroma. — The  circumstances  under  which  cartila- 
ginous and  osseous  structures  are  met  with  in  the  uterus,  are  similar  to 
those  which  condition  the  occurrence  of  fatty  tissue  in  this  organ,  where 
such  structures  are  always  heterotopic.  In  the  cervix  of  an  otherwise 
normal  foetal  uterus,  R.  Meyer  *  found  a  bony  nodule,  closely  associated 
with  a  vestige  of  the  Wolffian  duct,  through  the  medium  of  which  it  had 
evidently  been  introduced  ab  extra  (Fig.  7).  In  this  connexion,  it  is  of 
interest  to  note  that  bone-  and  cartilage-containing  tumours  arise  more 
frequently  from  this  part  of  the  uterus  than  elsewhere.  This  is  specially 
obvious  with  regard  to  the  peculiar  forms  of  "mixed"  sarcomata,  to  which 
this  part  is  prone,  whose  structure  comprises  such  various  heterotopic 
structures,  as  cartilage,  bone,  striped  muscle,  fat,  mucous  tissue,  epithelial 
elements  etc.,  of  which  so  many  instances  have  been  reported  ;  and  I 
think  there  can  be  no  doubt,  that  the  germs  of  these  tumours  are  aberrant 
elements  sequestrated  from  the  matrix  of  adjacent  tissues  during  early 
pre-natal  life.  I  have  cited  many  examples  of  this  kind,  in  my  books  on 
Uterine  and  on  Vaginal  Tumours.  Gebhard  has  met  with  a  malig- 
nant epithelial  growth  of  this  vicinity,  whose  stroma  was  studded  with 
bits  of  hyaline  cartilage.  If  malignant  tumours  of  this  locality  were 
carefully  examined,  in  serial  sections,  ad  hoc,  it  would  probably  be  found 
that  aberrant  elements  of  this  kind  are  not  particularly  rare. 

1  "Knocheoherd  in  der  Cervix  eines  foetalen  Uterus,"  Arch.  f.  path.  Anat.,  1902. 
Bd.  clxvii.,  S.  81. 


THE  GENESIS  OF  MALIGNANT  TUMOURS  149 

Even  as  long  ago  as  1849,  Lebert  had — in  two  specimens — demon- 
strated the  presence  of  true  bone  in  uterine  myomata  ;  and,  at  about  the 
same  period,  J.  H.  Bennet  found  cartilage  ;  similar  finds  have  since  been 
made  by  Henle,  Bidder,  Freund,  Ascher,  Feuchtwanger,  Johnston,  and 
others  ;  so  that  the  occurrence  of  this  kind  of  heterotopia  is  established 
beyond  cavil.  The  only  possible  scientific  explanation  of  such  conditions, 
is  the  inclusion  of  osteo-  and  chondro-blasts  in  the  nascent  myomata,  by 
sequestration  from  adjacent  parts  during  early  foetal  life. 

In  like  manner,  the  remarkable  proneness  of  uterine  myomata  to 
fibrification  and  calcification,  probably  depends  upon  the  inclusion  of 


FIG.  7.— A  NODULE  OF  BONE  IN  THE  CERVIX  OF  AN  OTHERWISE  NORMAL  F<ETAL 
UTERUS  (R.  MEYER). 


Transverse  Section  of  the  Pelvic  Organs  under  a  low  magnifying  power. 

t's  pouch ;  U,  uterus ;  K,  nodule  of  boi 
obliterated  Wolffian  duct ;  V,  bladder. 


R,  Rectum ;  D,  Douglas's  pouch ;  U,  uterus ;  K,  nodule  of  bone  in  the  vicinity  of  the 

"blite 


heterotopic  fibrinogenous  and  sclerogenous  elements  ab  extra  ;  for  such 
proclivities  are  foreign  to  the  normal  uterine  musculature. 

The  occurrence  of  osseous  and  chondromatous  tumours  in  the  uterus 
— of  which  instances  have  been  reported  by  Miller,  Seydel  etc. — can  only 
be  interpreted  on  similar  lines.  In  Miller's  case,  an  osseous  tumour 
occupied  the  site  of  the  corpus  of  a  malformed  uterus,  the  patient  being 
a  girl,  sixteen  years  old,  in  whom  the  vagina  was  absent. 

Here  it  should  be  noted,  that  osseous  and  cartilaginous  structures  are 
also  sometimes  met  with  in  sarcomatous  tumours  of  the  uterus,  other 
than  those  peculiar  forms  above  referred  to,  of  which  instances  are  given 
in  my  book  on  "  Uterine  Tumours." 


150  THE  NATURAL  HISTORY  OF  CANCER 

Bone  and  cartilage-containing  tumours  have  also  been  met  with  in 
the  vicinity  of  the  uterus,  e.g.,  in  the  ovary  (Baet,  Barnes,  Donati,  etc.), 
in  the  broad  ligament  (Kaul-chondrifying  sarcoma),  and  in  the  recto- 
uterine  cul-de-sac  (Hugenberger). 

Cysts. — Very  interesting  in  this  connexion  is  the  little-studied  subject 
of  cyst-genesis  in  the  uterus  ;  for,  nearly  all  formations  of  this  kind  un- 
doubtedly arise,  as  the  outcome  of  pre-natal  developmental  irregularity. 

The  discovery  of  aberrant  epithelial  inclusions  of  various  kinds  in  the 
uterine  wall  and  its  vicinity,  to  which  I  have  previously  referred,  enables 
us  to  understand  the  sources  whence  many  uterine  cysts  arise.  These 
heterotopic  elements  have  been  described  by  various  authors  as  of  Wolffian, 
Miillerian  and  mucosal  origin  ;  and  probably  all  these  sources  are  repre- 
sented in  the  germs  of  uterine  cysts.  As  many  recent  researches  have 
shown,  the  track  of  the  uro-genital  anlage  is  strewn  with  debris  of  this 
kind. 

The  commonest  uterine  cysts  undoubtedly  are  the  small  multiple  ones 
of  the  cervix  and  its  vicinity,  which  only  occasionaUy  increase  to  such  a 
size  as  to  merit  the  name  of  disease.  The  histological  structure  of  these 
cysts,  as  well  as  the  peculiar  nature  of  their  fluid  contents,  enable  us  to 
recognize  their  identity  with  the  glands  of  the  cervix,  of  which  they  are 
obviously  sequestrations.  The  well-known  ovula  Nabothii  are  the 
prototypes  of  these  cysts,  which  R.  Meyer  has  discriminated  in  the  pre- 
natal period. 

In  the  antero-lateral  part  of  the  cervix  and  the  adjacent  parts  of  the 
uterus,  cysts  are  occasionally  found — lined  by  a  single  layer  of  cubical 
epithelium  quite  different  from  that  of  the  glands  of  the  cervix — which, 
it  appears  certain,  are  derived  from  the  cystic  distension  of  unobliterated 
portions  of  the  Wolffian  duct  (Gartner's),  such  as  Meyer,  Nagel,  Tourneux, 
Rieder,  and  others,  have  discovered  in  this  vicinity.  In  pre-natal  life. 
Meyer  found  that  these  vestigial  remains  were  more  extensive,  and  of  more 
frequent  occurrence,  than  after  birth.  Cysts  of  this  kind — some  of  them 
congenital — have  been  studied  by  Burckhardt,  Senn,  Klein,  Rieder  and 
many  others. 

*  We  are  indebted  to  the  admirable  researches  of  Coblenz,1  the  signifi- 
cance of  which  are  even  nowT  not  fully  appreciated,  for  recognition  of  the 
fact  that  papilliferous  cysts  may  develop  anywhere  along  the  course  of  the 
Wolffian  (Gartner's)  ducts  ;  and  he  has  also  shown  that  the  germs  whence 
these  cysts  arise  are  Wolffian  residua — derivatives  of  the  paroophoron, 
or,  as  is  rarer,  of  the  epoophoron.  The  work  of  Recklinghausen,  Meyer, 
Pick,  Landau  and  others,  confirms  and  extends  Coblenz'  results. 

Residua  of  this  kind  have  been  detected  in  the  otherwise  normal 
uterine  musculature  by  Coblenz,  Ricker,  Rieder,  Meyer,  and  others  ; 
and,  in  the  adjacent  structures — e.g.,  broad  ligament,  round  ligament, 
pelvic  connective  tissue,  tube,  ovary  etc. 

As  examples  of  cystic  tumours  arising  in  the  uterine  walls  from  these 
Wolffian  residua,  reference  may  be  made  to  Czerwenka's  case  of  <;  cyst- 
adenoma  papillare  proliferans  "  ;  to  Gusserow's  case  of  "  cystic  adenoma  "  ; 
to  Ahlf eld's  case  of  "  kystoma  multiloculare  "  of  the  cervix  and  portio 
1   Arch.  f.  path.  Anat.,  1881,  Bd.  Ixxxiv.,  S.  26. 


THE  GENESIS  OF  MALIGNANT  TUMOURS  151 

etc.,  as  well  as  to  older  cases  of  like  nature  reported  by  Cruveilhier,  Lebert 
and  Rokitansky.  Meyer  has  met  with  a  large  congenital  tumour  of  this 
type,  in  an  eight-month  foetus,  which  had  evolved  in  close  proximity  to 
Gartner's  duct. 

A  congenital  polycystic  condition  of  the  corpus  uteri,  with  cystic 
adeno-myoma  of  the  cervix,  has  been  described  by  Woskresensky  ;  and 
Mears1  has  reported  a  remarkable  case  in  which  congenital  polycystic 
changes  affected  the  uterus,  ovaries,  and  kidneys  simultaneously,  as  if 
owing  to  some  developmental  irregularity  affecting  the  evolution  of  the 
whole  Wolffian  body. 

Similar  cystic  papilliferous  tumours  have  been  met  with  in  the  vagina, 
in  the  para-uterine  and  para-vaginal  connective  tissue,  in  the  broad 
ligaments,  round  ligaments  etc. 

Here  also  mention  may  be  made  of  the  fact,  that  in  nearly  all  of  the 
above-mentioned  localities  myomatous  tumours,  comprising  well-marked 
Wolffian  residua — the  so-called  "  mesonephric  myomata  " — have  lately 
been  discriminated. 

Since  these  papilliferous  and  other  cystic  tumours  are  identical  in 
structure  with  the  ordinary  forms  of  ovarian  cystoma,  the  important 
inference  may  be  drawn,  that  these  ovarian  cysts  also  arise  from  included 
Wolffian  residua  ;  as  to  which  it  seems  to  me  the  cumulative  evidence 
from  various  sources  is  so  strong,  as  to  be  practically  conclusive.  And 
in  the  same  category,  I  doubt  not,  congenital  polycystic  disease  of  the 
kidneys  should  be  included.  It  would  require  more  space  than  is  here 
available  to  fully  prove  this  thesis  ;  but  I  have  at  hand  all  the  evidence 
for  doing  so.  As  an  indication  of  the  correctness  of  this  interpretation, 
reference  may  here  be  made  to  the  obvious  correspondence  between  the 
different  forms  of  ovarian  and  broad-ligament  cysts,  which  holds  good 
even  for  dermoids. 

Dermoids. — The  researches  of  Sanger  have  made  it  perfectly  clear, 
that  dermoids  do  originate  in  the  pelvic  connective  tissue  and  adjacent 
structures,  quite  independently  of  the  ovaries.  Thus,  formations  of  this 
kind  have  been  found  in  the  pelvic  connective  tissue  (Hofer,  Germain, 
Sanger)  ;  between  the  vagina  and  rectum  (Mahomed,  Mannel,  Merriman)  ; 
between  the  cervix  uteri  and  rectum  (Emmet,  Cartez,  Barette,  Beyea)  ; 
between  the  bladder  and  uterus  (Kiister,  Sanger,  Charcot)  ;  in  the  urethro- 
vaginal  septum  (Englisch,  Wiggin)  ;  in  the  tube  (Pozzi,  Treub,  Ritchie, 
Orthmann)  ;  in  the  broad  ligaments  (Abel,  Marshall,  Lunn,  Gottschalk, 
Rendu,  Hofer  etc.)  ;  in  the  round  ligament  (Rendu)  ;  in  the  vagina 
(Watts,  Veit)  ;  while  in  the  bladder  and  rectum  many  such  cases  have  been 
reported. 

In  several  of  the  sites  of  these  pelvic  dermoids,  ectodermal  "  rests  " 
have  been  detected  in  foetal  or  early  post-natal  life  ;  e.g.,  in  the  broad 
ligaments  by  Meyer,  Switalski,  Ribbert  (Fig.  8,  next  page),  and  March- 
and  ;  in  the  pelvic  connective  tissue  (especially  in  and  in  the  vicinity  of 
the  lymph-glands)  by  Wakefield  ;  in  the  musculature  at  the  neck  of  the 
bladder  by  Meyer  etc. 

I  am  not  aware  that  extrinsic  ectodermal  elements  of  this  kind,  have 
1  Philadelphia  Medical  Times,  U.S.,  1872,  p.  314. 


152 


THE  NATURAL  HISTORY  OF  CANCER 


hitherto  ever  been  detected  in  the  otherwise  normal  uterine  parenchyma  ; 
but  it  is,  nevertheless,  tolerably  certain,  if  the  cervix  were  systematically 
examined  ad  hoc,  that  such  would  be  found.  The  presence  of  epidermoidal 
elements  in  certain  sarcomata  of  the  lower  part  of  the  uterus,  as  in 
cases  described  by  Hauser,  Rosenstein  etc.,  points  to  this  conclusion  ; 
and  of  like  significance  is  the  occurrence  of  melanotic  elements  in  sarcomata 
of  this  part,  as  described  by  Whitridge  Williams,  Johnston  etc.,  and  in  a 
uterine  myoma  by  Evelt. 

Very  little  is  to  be  found  in  pathological  publications,  as  to  uterine 
dermoids  ;  indeed,  until  Sanger  (1890)  had  made  it  perfectly  clear  that 
these  formations  do  originate  in  the  pelvic  connective  tissue,  quite  inde- 


FIG.  8. — A  HETBKOTOPIC,  HORNIFYING,  EPIDERMOIDAL  "REST"  IN  THE  BROAD 
LIGAMENT  (RIBBERT). 

E,  The  aberrant  epidermoidal  nodule ;    B,  Connective  tissue  of   the  broad  ligament ; 
O,  ovary ;  W,  W,  Wolffian  tubules. 

pendently  of  the  ovaries,  the  possibility  of  such  occurrences  was  generally 
disbelieved.  With  such  facts  as  those  above  cited  before  us,  it  would, 
however,  now  be  unreasonable  to  maintain  such  a  sceptical  attitude. 
In  comparatively  recent  times,  examples  of  the  simplest  form  of  uterine 
dermoid  cyst,  with  sebaceous  or  cholesteatomatous  contents,  have  been 
studied  by  Ahlfeld,  Cornil,  Allen,  French,  Recklinghausen,  and  Shoe- 
maker ;  in  the  older  publications,  examples  of  somewhat  more  complicated 
forms  (piliferous)  are  recorded  by  Vicq  d'Azyr  and  Fabricius  Hildanus  ; 
and,  in  recent  times,  teeth  and  hairs,  as  in  Stewart's  case  ;  while,  a  few 
years  ago,  a  still  more  complicated  tumour  of  this  kind  was  described  by 
Geyl  i1  this  formation  was  connected  with  the  posterior  part  of  the  vaginal 
fornix,  and  besides  skin,  it  comprised  such  diverse  structures  as  bone, 
striped  muscle,  fat,  nerve  etc. 

At  an  early  stage  of  pre-natal  development,  the  Wolffian  duct  is  in 
1  SammL.  klin.  Vortrage,  N.F.,  No.  190,  1897. 


THE  GENESIS  OF  MALIGNANT  TUMOURS  153 

such  close  proximity  to  the  ectoderm,  that  many  embryologists  now 
maintain  its  ectodermal  origin.  However  this  may  be,  it  is  certain  that 
in  its  subsequent  migration,  this  duct  may  carry  away  with  it  ectodermal 
elements,  which  may  thus  be  lodged  in  the  uterus,  pelvic  connective 
tissue,  ovary  or  other  pelvic  organs,  where  dermoid  cysts  have  been  found. 
It  is  to  foreign  elements  thus  imported  during  early  pre-natal  life,  that 
we  must  ascribe  the  germs  of  these  various  dermoid  tumours. 

Ovarian  and  other  dermoids  are  known  to  have  marked  proclivity 
to  originate  malignant  disease,  but  hitherto  no  instance  of  this  kind 
has  been  reported  in  connexion  with  these  pelvic  dermoids,  unless  an  old 
case  by  J.  S.  Bedford  :  -;  Sarcomatous  Tumour  of  the  Uterus  containing 
Hairs  and  Stearine,"  is  of  this  nature  ;  but  several  examples  of  primary  v/ 
malignant  epithelial  and  connective-tissue  tumours  of  the  pelvic  areolar 
tissue,  obviously  of  heterotopic  origin,  have  been  met  with  (Heinsius, 
Herff,  W.  M.  Smith  and  Kaul — chondro-sarcoma). 

The  probable  origin  of  certain  uterine  and  vaginal  tumours  from 
"  rests  "  of  the  Miillerian  ducts,  that  have  failed  to  fuse  and  blend  in  the 
formation  of  the  utero-vaginal  canal,  was  first  suggested  by  Freund. 
He  described  myomatous  cystic  tumours  of  this  kind,  as  occurring  in  the 
lower  part  of  the  uterus  and  the  upper  part  of  the  vagina,  especially 
posteriorly. 

Similar  formations  have  been  met  with  in  the  para-uterine  con- 
nective tissue  (Verneuil,  Haussmann).  A  single  layer  of  columnar 
epithelium,  which  is  often  ciliated  and  may  present  involutions  and 
cysts,  lines  the  interior  of  these  tumours.  There  are  generally  traces 
of  concomitant  uterine  duplicity,  e.g.,  uterus  bicornis  septus  etc.  In- 
stances of  congenital  tumours  of  this  kind  have  been  reported  by  Briesky, 
and  others. 

Myomatous  uterine  tumours,  having  in  their  interior  diverticula 
communicating  with  the  uterine  cavity,  as  in  cases  of  uterus  accessorius — 
bifid,  trifid  uterus  etc. — have  also  been  reported  (Brens,  Neugebauer, 
Ricker,  Recklinghauseh,  Meyer,  Hollander,  Skene,  Delpage  and  others). 
Such  conditions  appear  to  be  due  to  abnormal  myomatous  growth, 
around  persistent  diverticula  from  the  Miillerian  ducts  of  pre-natal 
origin.  Tumours  of  this  kind  are,  however,  far  from  common;  and* it 
seems  to  me  improbable  from  consideration  of  the  ensemble  of  the  subject, 
that  the  ordinary  myomata  arise  from  Miillerian  "  rests."  In  this  con- 
nexion it  should  be  borne  in  mind,  that  the  Miillerian  ducts  have  no  proper 
musculature  of  their  own,  the  elements  whence  this  is  derived  being 
superimposed  ab  extra. 

Another  form  of  uterine  cyst,  of  which  many  examples  have  been 
recorded  (Leopold,  Fehling  etc.),  is  the  endothelial-lined  formation, 
which  is  generally  believed  to  be  of  lymph- angiectasic  or  telangiectasic 
origin.  It  is  well,  however,  to  recollect  that  Meyer  specially  noted  the 
frequent  invagination  and  inclusion  of  small  peritoneal  pouches,  into  the 
nascent  uterine  wall  during  pre-natal  life  ;  and  it  is  probable  that  these 
inclusions  are  the  germs  whence  most  cysts  of  this  kind  originate.  It 
accords  with  this  mode  of  origin,  that  Hahnsseau  has  lately  reported 
instances  of  this  variety  of  cyst,  caused  by  the  traumatic  inclusion  o 


154  THE  NATURAL  HISTORY  OP  CANCER 

peritoneum  in  wounds  made  during  operations  on  the  uterus  and  its 
adnexa. 

Sarcoma. — In  the  foregoing  dissertation,  I  have  proved  that  the 
germs  of  all  non-malignant  uterine  tumours  are  the  outcome  of  develop- 
mental irregularity,  during  pre-natal  life.  Did  time  and  space  permit,  I 
could  adduce  equally  conclusive  proof,  that  the  anlagen  of  all  non- 
malignant  tumours — wherever  arising — are  similarly  conditioned. 

This  being  so,  an  a  priori  assumption  is  inevitably  raised,  that  the 
germs  of  malignant  tumours  may  also  be  similarly  conditioned.  Hence 
we  now  have  to  focus  our  attention  on  this  aspect  of  the  subject,  so  far 
at  least  as  malignant  tumours  of  the  uterus  are  concerned. 

I  have  already  had  occasion  to  indicate  several  instances  in  which  the 
heterotopic  findings,  revealed  by  histological  analysis  of  tumours  of  this 
kind — together  with  other  facts  of  like  import — pointed  clearly  to  pre- 
natal origin  ;  and  most  of  these  tumours  were  sarcomatous. 

Taken  as  a  whole,  a  surprisingly  large  proportion  of  uterine  sarcomata 
are  found,  on  careful  examination,  to  bear  the  impress  of  the  pre-natal 
stamp. 

Practically  all  of  the  important  group  of  "  infantile  "  sarcomata 1 — 
whether  of  the  lower  part  of  the  uterus  or  of  the  vagina — must  be 
included  in  this  category.  These  tumours  are  often  congenital,  or  they 
occur  very  early  in  life  ;  they  are  frequently  multiple  db  initio,  and 
accompanied  by  multiple"  polypi ;  while  other  adjacent  organs,  besides 
the  one  primarily  involved,  may  be  concurrently  affected.  Their 
structure  commonly  comprises  various  heterotopic  elements,  such  as 
striped  muscle  cells,  epithelial  islets,  leiomyomatous  cells  and  myomatous 
tissue.  These  various  indications  point  conclusively  to  their  origin  from 
pre-natal  developmental  irregularities  ;  and  it  should  be  noted  that  of 
the  parts  apt  to  be  involved,  all  are  more  or  less  concerned  in  the  for-  , 
mation  of  the  cloaca  ;  indeed,  it  is  with  the  formation  of  this  structure — 
even  more  than  with  that  of  the  uterus — that  the  germs  of  this  curious 
disease  originate  by  sequestration  and  inclusion,  during  the  various 
processes  of  approximation  and  fusion  of  the  constituent  parts  involved 
therein. 

'Another  considerable  group  of  uterine  sarcomata,  which  recent 
research  has  shown  to  be  much  less  rare  than  was  formerly  believed,  is 
the  grape-like  or  botryoidal  variety  of  adults  ;  which  is — with  few  excep- 
tions— a  malady  of  the  lower  part  of  the  uterus.  In  this,  as  in  some 
other  respects,  the  malady  resembles  the  infantile  variety ;  but,  unlike 
the  latter,  initial  multiplicity — especiaUy  in  adjacent  organs  such  as  the 
vagina,  bladder  and  rectum — is  hardly  ever  seen.  Hence  it  may  be 
inferred  that  the  developmental  irregularity  concerned  in  its  genesis, 
appertains  to  the  cervix  proper  rather  than  to  the  cloaca.  With  this 
reservation,  the  difference  in  age  incidence,  and  also  the  different  nature 
of  the  concomitant  heterotopic  inclusions,  e.g.,  cartilage  and  bone, 
these  two  forms  of  disease  have  much  in  common. 

The  structure  of  this  peculiar  type  of  sarcoma  commonly  comprises 

1  For  details  of  illustrative  cases  the  reader  is  referred  to  my  publications  on  "  Uterine 
Tumours,"  p.  322,  and  on  "  Vaginal  Tumours,"  p.  25. 


THE  GENESIS  OF  MALIGNANT  TUMOURS  155 

such  various  heterotopic  constituents  as  striped  muscle,  cartilage,  bone, 
various  types  of  epithelial  elements,  mucous  tissue  etc. ;  which,  it  may 
be  inferred,  from  what  I  have  previously  mentioned  as  to  the  develop- 
mental anomalies  of  this  part,  arise  from  aberrant  elements  sequestrated 
from  the  matrix  of  adjacent  tissues  during  pre-natal  life,  and  included 
in  the  nascent  organ,  probably  through  the  agency  of  the  Wolffian  duct 
in  most  cases. 

Judged  by  the  results  of  their  histological  analysis  and  general  mor- 
phology, the  remaining  uterine  sarcomata  may  be  regarded  as  derivatives 
of  the  mucosa,  or  of  the  parenchyma  of  the  uterine  wall.  As  to  the  pre- 
natal origin  of  the  germs  of  these  mucosal  tumours,  we  have  only  a  few 
— but  significant — indications  ;  e.g.,  Wagner,  Geissler  and  Reid  have  found 
chondromatous  structures  in  them ;  Whitridge  Williams,  Johnston, 
Taylor,  Rokitansky  and  others,  melanotic  elements,  which  can  only  be 
accounted  for  as  ectodermal  inclusions.  As  to  the  occasional  association 
of  tumours  of  this  kind  with  various  gross  uterine  malformations,  I  shall 
have  to  refer  to  it  in  the  sequel.  With  regard  to  the  sarcomata  of 
parenchymatous  origin,  some  of  these  undoubtedly  arise  from  myomata 
—which,  as  we  have  seen,  are  of  pre-natal  origin  ;  and,  in  this  connexion, 
we  must  not  forget  Evelt's  case  of  malignant  melanoma  primarily  arising 
in  a  myoma,  to  which  reference  has  previously  been  made.  Moreover, 
in  these  tumours  cartilaginous  and  epithelial  "  rests  "  are  occasionally 
found,  which  could  only  have  originated  during  pre-natal  life.  It  is  to 
this  latter  source,  that  we  must  refer  the  germs  of  the  various  remarkable 
cystic  sarcomata  of  parenchymatous  origin  ;  thus,  in  a  case  by  Aslanian, 
a  large  multilocular,  telangiectasic  cysto-sarcoma  of  this  kind,  was 
concomitant  with  abnormal  persistence  of  the  Wolffian  body  ;  while 
Coblenz  has  seen  sarcoma  of  the  uterine  parenchyma  concomitant  with  a 
unilocular  papillary  cyst  of  the  right  ovary,  and  multilocular  cystic 
disease  of  the  left  ovary. 

Of  like  import  are  the  cases  of  mixed  malignant  tumours — forms  in 
which  epitheliomatous  and  sarcomatous  processes  go  on  simultaneously — 
of  which  instances  have  been  reported  in  the  uterus  by  H.  K.  Spencer, 
Maier,  Kuhnart  etc. 

Taking  all  these  various  indications  into  consideration,  it  seems  to 
me  impossible  to  avoid  the  conclusion,  that  the  germs  of  all  uterine 
sarcomata  are  probably  the  outcome  of  developmental  irregularity  of 
pre-natal  origin. 

Malignant  Epithelial  Tumours. — From  what  has  been  previously  stated. 
it  will  be  gathered  that  histioid  tumours  are  never  of  such  a  monstrous 
nature,  as  not  to  present  some  analogy  to  the  pre-existing  structure 
of  the  parts  whence  they  originate,  either  in  their  pre-  or  post-natal 
states  ;  and  this  holds  also  for  malignant  epithelial  tumours,  as  I  shall  now 
proceed  to  show.  Moreover,  it  is  not  only  the  constituent  cells  of  these 
tumours,  wherein  the  essence  of  the  disease  resides,  that  manifest  this 
similitude  ;  but  also  the  connective-tissue  stroma  or  framework,  wherein 
they  are  set.  Thus  may  be  explained  the  great  structural  diversities, 
that  obtain  between  the  malignant  epithelial  tumours  of  different  parts, 
and  of  different  tissues,  according  to  the  sites  whence  they  originate, 


156  THE  NATURAL  HISTORY  OF  CANCER 

which  is  such  a  marked  feature  of  all  tumours  of  this  kind.  What,  for 
instance,  can  be  more  divergent  in  this  respect,  than  the  appearances 
presented  on  microscopical  examination  by  sections  of  cancers  from 
such  different  parts  as  the  breast,  the  rectum  and  the  skin  ?  We  learn 
from  such  studies,  that  malignant  epithelial  new  formations  always 
present  unmistakable  histological  resemblance  to  the  structures  whence 
they  originate.  And  this  resemblance  can  also  be  traced  in  the  physio- 
logical properties  of  their  constituent  cells ;  for,  as  Waring  x  has  demon- 
strated, the  cells  of  cancer  of  the  stomach  and  pancreas  produce  the 
same  ferments — pepsin,  trypsin,  etc. — as  the  normal  secretory  cells  of 
these  organs.2  In  like  manner,  Johannes  Miiller,  more  than  half  a  century 
ago,  proved  the  presence  of  casein  in  cancers  of  the  female  breast ;  and 
the  abundance  of  fatty  matters  contained  in  the  cells  of  these  neoplasms 
is  well  known.  We  are  thus  reminded  of  the  similar  metamorphoses  that 
the  cells  of  the  normal  gland  undergo  during  lactation  ;  but,  the  nearest 
approach  to  normal  secretion,  that  the  tumour  structure  ever  produces  is 
a  scanty  mucoid  fluid,  presenting  some  resemblance  to  a  poor  kind  of 
colostrum.  Such  a  result  is  quite  in  accordance  with  the  experiments  of 
Martinotti,  which  show  that  the  cells  of  secretory  glands  when  in  a  state 
of  active  growth  and  proliferation,  tend  to  lose  their  normal  secretory 
aptitudes — there  being  a  certain  antagonism  between  proliferative  and 
secretory  changes. 

Similarly,  cancers  of  the  cervix  uteri  may  be  expected  to  yield  indica- 
tions of  the  presence  of  substances  identical  with  the  cervical  mucus  ; 
and,  in  this  respect,  they  will  probably  be  found  to  differ  from  cancers 
of  the  corpus.  As  tending  to  confirm  this  expectation,  it  may  be  men- 
tioned that  Cornil  and  others  have  observed,  in  the  constituent  cells  of 
cervical  cancers,  indications  of  mucoid  or  calyciform  changes,  similar  to 
those  that  are  so  characteristic  of  the  epithelium  of  the  cervical  glands 
during  the  elaboration  of  their  peculiar  secretion. 

The  cornifying  properties  of  epidermoidal  cancers  of  the  skin,  likewise 
exemplify  the  same  peculiarity. 

The  characteristics  of  the  stroma  of  cancerous  tumours,  are  chiefly 
determined  by  the  pre-existing  structure  of  the  affected  part.  Its 
alveolar  disposition,  which  was  formerly  regarded  as  the  histological 
criterion  of  cancer,  is  now  known  to  be  merely  a  local  peculiarity. 

In  its  minute  structure  and  general  characters,  the  stroma  of 
mammary  cancer  closely  resembles  the  stroma  of  the  normal  gland,  of 
which  it  is  evidently  a  derivative.  It  consists  of  thick  bands  of  dense 
white  fibrous  tissue,  containing  elastic  fibres  and  anastomosing  con- 
nective-tissue cells,  which  are  specially  numerous  at  the  meeting-points 
of  the  diverging  bands.  The  characteristic  hardness  of  mammary 
cancer  is  mainly  due  to  its  abundance  and  density  ;  in  fact,  hard  cancers 
are  the  dominant  forms  that  arise  from  regions  rich  in  fibrous  tissue. 
Moreover,  it  is  noticeable  that  elastic  fibres  are  met  with  in  great  abund- 
ance in  cancers  that  arise  from  structures  normally  rich  in  them,  such 

1  Journal  of  Anatomy,  October,  1893,  p.  142. 

2  In  pancreatic  cancers,  besides  trypsin,  Waring  found  amylopsin,  steapsiu,  and  a 
milk-curdling  ferment. 


THE  GENESIS  OF  MALIGNANT  TUMOURS  157 

as  the  breast  and  skin.  Miiller  attributes  the  large  amount  of  gelatin 
found  on  analysis  in  mammary  cancers,  to  the  abundance  of  its  fibrous 
stroma. 

On  the  other  hand,  the  stroma  of  uterine  cancers  consists  of  scanty 
fibrillar  tissue,  like  that  met  with  in  the  normal  uterine  mucosa,  which  it 
further  resembles  in  that  it  usually  contains  unstriped  muscle  cells. 
Hence  little  or  no  gelatin  is  found  in  uterine  cancers. 

Another  marked  characteristic  of  cancerous  tumours  that  must  be 
mentioned  here,  is  the  great  resemblance  always  noticeable  between  the 
primary  and  secondary  growths,  the  significance  of  which  it  is  impossible 
to  ignore.  As  Moxon  has  sagely  remarked  :  "  The  first  cancer  which 
appears  has  a  likeness  to  the  part  in  which  it  appears,  and  the  secondary 
cancers  arising  from  it  have  the  likeness  of  that  first  cancer  ;  and  those 
who  doubt  that  they  come  from  that  first  cancer  must  show  us  why 
they  have  that  likeness."  In  this  connexion  Waring's  observations  are 
of  great  interest,  for  they  show  that  the  same  physiological  properties 
are  manifested  by  the  cells  of  the  secondary,  as  by  those  of  the  primary 
growths.  In  short,  the  secondary  growths  repeat  the  distinctive 
characters  of  the  primary  growth  with  such  fidelity,  that  the  seat  of  the 
latter  may  often  be  correctly  surmised  by  careful  examination  of  the 
former. 

Bearing  in  mind  these  considerations  and  what  they  imply,  we  are 
now  in  a  position  to  come  to  closer  quarters  with  the  question  of  the 
genesis  of  uterine  cancer. 

Insuperable  difficulties  surround  the  investigation  of  the  very  earliest 
stages  of  primary  cancer  formation  ;  but,  in  the  formation  of  secondary 
cancers,  nature  is  constantly  performing  the  miracle  of  cancer  genesis 
under  our  very  eyes,  and  in  a  manner  that  admits  of  scientific  investiga- 
tion. There  are  good  reasons  for  believing  that  primary  cancers  arise, 
exactly  as  do  these  secondary  formations  ;  so  that,  by  investigating  the 
latter,  we  may  be  able  to  elucidate  the  former. 

Now,  the  most  important  fact  revealed  by  the  study  of  the  origin  of 
secondary  cancer  is,  that  the  germ  whence  it  arises — which  must  be  very 
small — is  not  a  normal  constituent  of  the  affected  part,  but  an  intruder 
ab  extra.  Can  the  like  be  said  of  the  germ  of  primary  cancer  ?  The 
histological  analysis  of  primary  cancers  of  the  uterus  shows  that  the 
majority  of  these  tumours  consist  of  structures,  which  have  remarkable 
similitude  to  those  normally  comprised  in  the  mucosa  of  the  part ;  and 
from  this  it  follows,  that  the  germs  of  these  tumours  must  be  derivatives 
of  this  structure — whether  of  pre-  or  post-natal  origin. 

Thus,  the  only  kind  of  heterotopia  that  can  be  admitted  for  the  germs 
of  these  uterine  cancers,  is  a  local  heterotopia,  referable  to  developmental 
irregularity  of  the  mucosa  itself.  In  this  restricted  sense,  as  I  shall 
proceed  to  show,  the  germs  of  most  uterine  cancers  are  decidedly 
heterotopic,  that  is  to  say,  they  are  not  direct  derivatives  of  the  normally 
integrated,  pre-existing  cells  of  the  part. 

The  great  majority  of  uterine  cancers  arise  in  the  cervix  ;  and,  among 
these  tumours,  it  is  not  uncommon  to  meet  with  forms,  which,  on  histo- 
logical examination,  present  no  recognizable  similitude  either  to  the 


158  THE  NATURAL  HISTORY  OF  CAXCER 

glandular  or  to  the  epidermoidal  structures  of  the  cervical  mucosa.  The 
germs  of  some  of  these  tumours  may  be  as  truly  heterotopic,  as  those  of 
the  secondary  cancers  ;  that  is  to  say,  they  may  be  derived  from  ecto- 
dermal  elements  sequestrated  during  early  pre-natal  lifer  and  included  in 
the  nascent  uterus  with  the  Wolffian  duct ;  or,  it  is  even  conceivable, 
that  they  may  be  "  rests  "  of  this  latter  structure.  We  know  that 
tumours  of  this  kind  and  thus  derived,  do  form  in  parts  adjacent  to  the 
uterus,  such  as  the  pe.vic  connective  tissue  etc.  ;  and,  therefore,  it 
seems  not  unreasonable  to  infer  that  they  may  also  originate  thus  in  the 
uterus  itself.  It  may  even  be  surmised,  that  the  undue  proclivity  of 
this  part  of  the  uterus  to  malignant  epithelial  tumours,  is  explicable  in 
this  way. 

However  this  may  be,  the  fact  remains  that  the  histological  elements 
of  most  uterine  cancers  so  closely  resemble  those  normally  met  with  in 
the  uterine  mucosa,  that  we  may  classify  them  as  being  either  of  the 
cylinder-celled  or  epidermoidal  type,  v 

The  mucosa  of  the  uterine  cavity  is  lined  throughout  by  a  single  layer 
of  cylinder-shaped  epithelial  cells ;  and  the  innumerable  glands  which 
open  on  its  surface,  are  the  result  of  follicular  depressions  of  this  epithelial 
lining  into  the  sub-mucosa.  In  the  midst  of  this  cylinder-celled  epithelial 
lining  of  the  corpus  uteri,  small  islets  of  aberrant  epidermoidal  cells, 
have  often  been  detected  (Ries,  Zeller,  Schuchardt,  Fritsch,  Friedlander 
etc.);  and  probably  this  condition  is  fairly  common.  Once  this  fact  has 
been  grasped,  there  can  be  no  difficulty  in  recognizing  these  heterotopic 
elements,  as  the  germs  of  those  hornifying  epidermoidal  cancers  of  this 
part,  of  which  examples  have  been  reported  by  Gellhorn,  Ries,  Piering, 
Gebhard,  Keith,  Flaischlen,  Lohlein,  Emanuel,  Kaufmann  and  others.  In 
several  instances  of  initial  multiplicity,  epidermoidal  cancer  has  been 
found  coexistent  with  cylinder-celled  cancer  of  the  same  uterus  (Hofmeier, 
Winter,  Schauta  etc.)  ;  and  some  cases  have  been  reported,  in  which  the 
two  kinds  of  epithelium  were  associated  in  the  same  tumour  (Hirschmann). 

The  mucosa  of  the  cervix,  as  to  its  upper  two-thirds,  is  lined  by  a 
single  layer  of  cylindrical  epithelial  cells  ;  whereas,  a  laminated,  flattened, 
epidermoidal  type  of  epithelium — which  is  an  upward  extension  of  that 
covering  the  portio — lines  more  or  less  of  its  lower  part ;  at  least,  this  is 
the  usual  condition  in  multiparse,  in  whom  the  flattened  cells  of  the 
portio  are  prolonged  for  a  variable — often  considerable — distance,  within 
the  canalis  cervicalis.  It  is  probable  that  the  heterotopic  epidermoidal 
cells  found  in  the  mucosa  of  the  corpus,  are  detached  aberrant  offsets 
from  these  upward  extensions  of  the  portio  cells,  sequestrated  during 
pre-natal  life.  It  accords  with  this,  that  ViUiers  and  Therese  have 
demonstrated,  in  the  midst  of  the  cylinder- celled  lining  of  the  cervical 
mucosa,  detached  islets  of  epidermoidal  cells,  with  Malpighian  stratum 
etc.,  where  they  presented  as  whitish  plaques.  Such  no  doubt  are  the 
germs,  whence  the  considerable  number  of  epidermoidal-celled  cancers 
of  this  part  of  the  cervix  arise. 

In  its  structure,  the  lining  membrane  of  the  portio  differs  from  that 
of  the  rest  of  the  uterus,  resembling  rather  that  of  the  vagina.  Similarly 
in  its  proclivity  to  neoplasms,  it  likewise  takes  after  the  vagina.  As  the 


THE  GENESIS  OF  MALIGNANT  TUMOURS  159 

portio  projects  into  the  vagina,  it  is,  in  fact,  capped  by  an  upward 
extension  of  the  epidermoidal-celled,  dermo-papillary,  vaginal  lining 
membrane.  In  the  development  of  papillated  structures  like  the  portio, 
the  epidermis  plays  an  important  part.  It  causes  these  structures  to 
arise  by  processes  of  its  proliferous  cells,  growing  into  the  subjacent 
mesoblastic  corium.  In  this  process,  "  rests "  of  these  ingrowing 
epidermoidal  processes  are  commonly  sequestrated,  and  included  in  the 
nascent  corium  ;  where,  in  post-natal  life,  they  may  subsequently  be 
recognized  by  histologists  as  ''  pearls,"  or  other  non-integrated  epider- 
moidal structures.  Pre-natal  "  rests "  of  this  kind,  are  of  common 
occurrence  in  and  beneath  the  corium  of  the  portio  and  adjacent  struc- 
tures. As  we  have  seen,  epidermoidal  elements  of  this  kind  are  the 
germs  whence  many  cervical  and  some  corpus  cancers  arise ;  hence,  it 
may  be  inferred  that  it  is  to  this  source,  rather  than  to  the  normally 
integrated  elements  of  the  mucosa  of  the  portio,  that  we  must  look  for 
the  germs  of  most  epidermoidal  cancers  of  this  part. 

In  addition  to  this  variety  of  epithelioma,  other  forms  also  originate 
from  this  part  of  the  uterus.  Under  certain  pseudo-pathological  con- 
ditions, which  I  will  now  proceed  to  describe,  the  cylindrical  epithelium 
of  the  cervix  encroaches  upon  the  epidermis-covered  territory  of  the 
portio ;  and,  from  this  foreign  element,  cylinder-celled  cancers  arise, 
analogous  to  those  that  spring  from  the  cervix.  So  common  is  this 
invasion  of  the  portio,  that  the  majority  of  its  cancers  originate  from  this 
source. 

It  seems  probable  that  most  of  these  aberrant  elements,  are  the 
outcome  of  pre-natal  developmental  irregularities.  At  an  early  stage  of 
embryonic  life,  the  upper  part  of  the  vagina,  as  well  as  the  cervix,  is  lined 
by  cylindrical  epithelium.  In  the  subsequent  transformation  to  the 
flattened  variety,  minute  islets  of  the  original  cylindrical  cells  may  still 
persist  unchanged.  Klotz  and  others  have  demonstrated  conditions  of 
this  kind  in  adults  ;  while  Fischel  has  shown  that  in  young  infants, 
cylindrical  epithelium  is  usually  found  occupying  the  portio,  for  a  con- 
siderable distance  beyond  the  os  externum. 

An  analogous  condition  results  from  the  invasion  of  the  portio  by 
offsets  of  the  cervical  glands  (the  so-called  "  erosions  ")>.  which  so  fre- 
quently  appear  during  post-embryonic  life  in  consequence  of  hyper- 
plastic  changes  ;  as  well  as  from  the  somewhat  similar  state  that  ensues 
from  partial  prolapse  ("  ectropion  ")  of  the  cervical  mucosa — whether 
merely  the  result  of  tears  etc.,  during  parturition,  of  cystic  disease,  or 
of  other  pathological  states.  Moreover,  the  minute  cysts  ("  ovula 
Nabothii  ")  so  frequently  met  with  in  the  lower  part  of  the  uterus,  which 
are  obviously  sequestrations  from  the  glands  of  the  cervix,  must  also  be 
borne  in  mind,  for  cancers  have  been  shown  to  originate  from  them. 

Here  it  may  be  mentioned  that  Nichols  *  has  produced  cysts  of  this  \ 
kind  experimentally,  by  transplanting  grafts  of  the  uterine  mucosa  into 
various  situations. 

Recent  researches  indicate  that  these  acquired  forms  of  heterotopia, 
like  those  previously  mentioned,  are  also  really  of  pre-natal  origin,  the 
1  Third  Report  of  the  Croft  Cancer  Committee,  Boston,  U.S.,  1905,  p.  117. 


160  THE  NATURAL  HISTORY  OF  CANCER 

inherent  flaw  simply  being  made  manifest  by  the  supervention  of  other 
pathological  changes.  Even  "  lacerations  "  may  often  be  of  embryonic 
origin,  for  Fischel  has  demonstrated  the  occurrence  of  congenital  fissures, 
in  exactly  the  situations  usually  occupied  by  these  so-called  lacera- 
tions. 

From  the  foregoing  it  will  be  gathered,  that  in  all  cases  in  which  we 
have  been  able  clearly  to  trace  the  genesis  of  cancer  in  the  different  parts 
of  the  uterus — corpus,  cervix  and  portio — the  germs  of  such  tumours 
have  proved  to  be,  not  the  normally  integrated,  pre-existing,  epithelial 
cells  of  the  part ;  but  rather  non-integrated  "  rests,"  detached  from  their 
normal  connexions  during  pre-natal  life.  This  being  so,  we  are  I  believe 
fully  justified  in  assuming,  that  the  germs  of  all  malignant  epithelial 
uterine  tumours  are  similarly  conditioned  ;  indeed,  the  more  carefully  we 
consider  the  significance  of  the  ensemble  of  ascertained  facts  and  indica- 
tions as  bearing  on  this  subject,  the  more  strongly  is  the  truthfulness  of 
this  conception  impressed  upon  us. 

In  short,  I  think  there  can  be  no  doubt,  that  pre-natal  developmental 
irregularity  presides  at  the  genesis  of  all  uterine  tumours. 


Uterine  Tumours,  and  Gross  Developmental  Irregularity  of  the 
Uterus  etc. 

I  now  pass  to  the  consideration  of  the  connexion  between  uterine 
tumours,  and  certain  gross  developmental  irregularities  of  the  uterus  and 
other  parts,  with  which  these  tumours  are  fairly  often  concomitant.  In 
the  absence  of  the  requisite  data,  it  is  for  the  present  impossible  to  ascer- 
tain the  exact  proportion  of  cases  in  which  this  concomitancy  occurs. 
It  would,  however,  be  a  mistake  to  suppose,  on  account  of  the  com- 
paratively few  instances  of  this  kind  noted  by  the  older  gynaecologists, 
who  made  special  studies  of  uterine  malformations  (Kussmaul,  Fiirst 
etc.),  that  this  concomitancy  is  rare  ;  for,  in  those  days,  when  the  terato- 
logical  aspect  of  the  subject  was  the  only  one  in  the  specialist's  mind,  it 
is  hardly  likely  that  the  presence  or  absence  of  tumours  would  have 
attracted  much  attention.  It  accords  with  this,  that  of  six  specimens 
illustrative  of  uterine  malformations,  in  the  broad-minded  Cruveilhier's 
great  work,1  two  were  complicated  by  myomata  and  one  with  double 
ovarian  cystoma.  But  the  best  proof  of  all  is,  that  within  the  last  few 
years  over  a  hundred  instances  of  this  concomitancy  have  been  recorded. 
Hence,  it  seems  to  me  as  clear  as  it  possibly  can  be,  short  of  actual  demon- 
stration, that  these  developmental  irregularities  predispose  to  tumour 
formation. 

Myoma. — Uterine  duplicity  is  the  commonest  type  of  malformation 
concomitant  with  myomata  ;  and  some  idea  of  its  frequency  may  be 
gathered  from  the  fact,  that  without  any  attempt  at  an  exhaustive 
search,  I  have  gathered  notes  of  over  fifty  cases.  In  this  list  all  the 
different  grades  of  duplicity  are  represented,  from  the  most  complete 
type  as  represented  by  uterus  didelphys  (cases  by  Clay,  Galabin,  G.  B. 

1  Anat.  Path,  du  corps  humain,  1829-1833,  t.  i.,  liv.  iv.,  pi.  v. 


THE  GENESIS  OF  MALIGNANT  TUMOURS 


161 


Johnston,  Lewers,  Graverry,  Munde,  Lyle,  Pick  etc.),  to  the  least  as 
represented  by  uterus  introrsum  arcuatus  (Flatau).  But  most  cases  are 
met  with  in  uterus  bicornis,  which  is  the  commonest  variety  of  this  type 
of  malformation  (Foisy,  Falk,  Eberlin,  Doran,  Lockyer,  Gow,  Boni, 


Martin,  Meurer,  Gunsett,  Wagner,   Heinricius,   Cruveilhier,   Snegurieff, 
Gibson,  Clark,  Pauchet  etc.). 

In  an  interesting  case  by  Clay,1  double  uterus   and  vagina  was 
associated  with  uterine  myomata,  and  absence  of  one  kidney.     In  a 
1  Lancet,  1877,  vol.  ii.,  p.  87. 


162  THE  NATURAL  HISTORY  OF  CANCER 

v  uterus  didelphys,  Czerwenka J  found  two  myomata  of  the  left  corpus, 
concomitant  with  cancer  of  the  left  cervix. 

In  G.  B.  Johnston's  case,2  one  compartment  of  the  double  uterus 
contained  a  full-term  foetus,  which  was  delivered  by  Csesarean  section, 
while  the  other  compartment  was  merged  in  a  large  myoma,  which  was 
removed,  with  the  malformed  organ,  by  hysterectomy.  In  uterus 
bifidus,  Pauchet  found  right-sided  myoma,  with  left-sided  pregnancy. 

Pick  3  has  reported  cases  in  which  the  myomatous  tumour  lay  in  the 
septum,  between  the  bodies  of  the  two  uteri ;  and  other  cases  of  this  kind 
have  been  met  with  by  Lockyer,4  Clark,  J.  Schmidt  (adeno-myoma), 
Gunsett  etc.  In  these  cases,  the  germ  of  the  tumours  must  have  been  in 
position,  as  early  as  the  second  month  of  pre-natal  .life,  when  the 
coalescence  of  the  Miillerian  ducts  begins. 

Several  instances  of  the  development  of  myomata  in  the  unicorn 
uterus  have  also  been  reported  of  late  :  e.g.,  in  the  rudimentary  horn  by 
Routh,  Doran,  Mackenzie,  Romiti,  Mangiagalli  etc.  ;  in  the  developed 
horn  by  Bland-Sutton  ;  and  in  the  cervix,  which  was  replaced  by  a 
mesonephric  adeno-myoma,  by  Josephson  etc. 

In  some  of  the  foregoing  cases,  the  vagina  also  was  absent  or  atresiac 
(Mangiagalli,  Eberlin) ;  while  cases  reported  by  Martin,  Jenks  and  Guyot, 
were  concomitant  with  vaginal  absence,  the  uterus  being  normal. 

Uterine  myomata  have  also  been  found  in  association  with  con- 
genital atresia  of  the  uterus  (Dreykorn),  congenital  ante-flexion  (Thomas), 
in  the  "  infantile  "  uterus  (Keiffer)  ;  while  Jackson  has  reported  myomata 
of  an  atresiac  "  infantile  "  uterus,  in  which  cancer  was  also  present. 

But  the  most  remarkable  instance  of  this  type  known  to  me,  is  the 
case  reported  by  Lynds,5  in  a  woman  aged  forty-five,  with  a  large  myoma 
of  three  years'  duration,  occupying  the  site  of  the  absent  uterus ;  who 
had,  nevertheless,  lived  for  nineteen  years  in  wedlock  without  being 
aware  of  any  physical  defect,  although  she  had  never  menstruated  and 
had  never  been  pregnant.  It  was  found,  in  the  course  of  the  operation, 
that  the  vagina  also  was  absent,  as  well  as  all  the  uterine  appendages  ; 
and,  of  the  ovaries,  the  only  trace  was  a  small  rudiment  of  one. 

I  have  previously  referred  to  myomatous  tumours  connected  with 
such  malformations  as  uterus  accessorius,  bifid  and  trifid  uterus  etc. 

In  a  pseudo-hermaphrodite,  aged  fifty,  in  whom  the  female  type 
appeared  to  predominate,  Griiner  found  myomata  of  the  malformed 
uterus  ;  and,  in  another  person,  aged  forty-nine,  with  a  similar  defect, 
Howitz  met  with  a  tumour  the  size  of  a  cocoanut,  due  to  myomatous 
disease  of  the  unicorn  uterus.  In  the  latter  case  the  left  tube  was  absent, 
the  ovaries  were  represented  merely  by  small  nodules,  remains  of 
Gartner's  ducts  were  found  in  the  vaginal  walls,  and  there  was  hypo- 
spadias  with  hypertrophy  of  the  clitoris.  Neumann  has  described 
myomata  of  the  uterus  and  tube,  concurrent  with  Wolffian  "  rests  "  in 
both  ovaries  ;  and  Russell  has  reported  the  finding  of  Miillerian  relics  in 

1  Monats.  f.  Geb.  u.  Gyn.,  Bd.  xx.,  Heft  5. 

2  Trans.  Southern  Surg.  and  Gyn.  Association,  Richmond,  Va.,  U.S.,  1900. 

3  Monats.  f.  Geb.  u.  Gyn.,  October,  1897  ;  also  Arch.  f.  Gyn.,  1896,  Bd.  lii.,  S.  389. 

4  British  Journal  of  Obstetrics,  etc.,  1905,  vol.  vii.,  p.  172. 

6  Journal  of  the  Michigan  State  Medical  Society,  U.S.,  March,  1905,  p.  122. 


THE  GENESIS  OF  MALIGNANT  TUMOURS  163 

the  ovary,  whence  structures  like  utricular  glands  had  evolved,  resembling 
the  epithelial  inclusions  found  in  some  myomata.  Wetherill,  in  removing 
a  large  myomatous  uterine  tumour,  noticed  supernumerary  oviducts 
and  hydatids. 

This  leads  me  to  remark  on  the  frequency  with  which  uterine 
myomata  are  complicated  with  ovarian  cystomata  (often  bilateral), 
dermoids,  and  cysts  of  the  adnexa — broad  ligaments,  round  ligaments,  etc. 

Of  his  operated  uterine  myomata,  Pean  found  associated  ovarian 
cystomata  in  12-5  per  cent. ;  and  of  Winckel's  ovarian  cystoma,  18  per 
cent,  were  concurrent  with  myoma  uteri. 

In  a  remarkable  case  reported  by  Buffett,  the  combined  weight  of  the 
associated  tumours  amounted  to  no  less  than  216  pounds,  the  left 
ovarian  cystoma  weighing  180  pounds,  and  the  uterine  myoma  36  pounds. 

In  the  case  of  a  negress,  with  an  enormous  cystic  myoma  weighing 
135  pounds,  as  described  by  Stockard,  the  uterus  also  contained  several 
solid  myomata  ;  and  besides  there  was  a  small  myoma  of  the  left  Fallopian 
tube,  a  cyst  of  the  corresponding  broad  ligament,  and  cystic  disease  of 
the  left  ovary. 

Leo  has  found  myomata  of  the  uterus  coexisting  with  cystoma  of 
the  right  ovary,  and  polycystic  disease  of  the  left  kidney.  I  have 
previously  had  occasion  to  refer  to  Mear's  case,  in  which  the  uterus, 
ovaries  and  kidneys  were  concurrently  affected  with  congenital  poly- 
cystic  disease,  as  if  from  some  developmental  irregularity  involving 
the  whole  Wolffian  body.  Flatau  has  found  a  similar  type  of  cystic 
uterine  disease  concomitant  with  myoma  of  that  organ  ;  while  Doleris 
and  Algret  report  the  concurrence  of  uterine  myomata,  with  congenital 
polycystic  disease  of  both  kidneys. 

Thornton  has  seen  multiple  uterine  myomata  associated  with  a  large 
multilocular  cystoma  of  the  right  ovary,  a  cyst  of  the  right  broad 
ligament,  and  multiple  cysts  of  the  left  ovary  ;  and,  in  Hodge's  case, 
uterine  myomata  were  associated  with  cystic  disease  of  the  ovary  and 
broad  ligament. 

Dartigues  and  Claisse  have  reported  an  instance,  in  which  a  large 
uterine  myoma  coexisted  with  an  enormous  multilocular  cyst  of  the  left 
ovary,  and  a  dermoid  of  the  right. 

Emmet  has  seen  a  large  cystic  myoma  of  the  fundus,  with  several  sold 
myomata  adjacent  to  it,  and  a  polypoid  intra-uterine  myoma,  concomi- 
tant with  multilocular  cystoma  and  dermoid  of  the  right  ovary.  In 
many  cases,  uterine  myomata  and  ovarian  or  broad-ligament  dermoids, 
have  been  found  concomitant  (Porter,  Mauclaire,  Hulke,  Gottschalk  etc.). 

Amann  mentions  the  association  of  adeno-myoma  of  the  uterus  with 
ovarian  dermoid  ;  Cartez  has  found  uterine  myomatous  disease,  concomi- 
tant with  a  piliferous  dermoid  of  the  connective  tissue,  beneath  the 
peritoneum  of  Douglas's  pouch  ;  and  Berger  met  with  a  para-uterine, 
piliferous  pelvic  dermoid,  which  comprised  a  piece  of  bone  bearing  two 
teeth,  concomitant  with  myoma  of  the  corpus  uteri. 

Fatty  tumours  of  the  para-uterine  connective  tissue,  in  association 
with  myoma  uteri,  have  been  described  by  Roux  and  Ullman. 

Myomatous  tumours  of  the  uterus,  with  bipartite  bladder,  have  been 

11—2 


164  THE  NATURAL  HISTORY  OF  CANCER 

reported  by  Knox  ;  and  by  Garrigues,  the  same  disease  has  been  seen 
with  the  foetal  type  of  bladder.  Thorne  found  uterine  myomata 
coexistent  with  ossifying  myoma  of  the  bladder. 

The  frequency  with  which  uterine  myomata  are  multiple,  might  of 
itself  lead  us  to  suspect  the  association  of  developmental  irregularity, 
with  the  origin  of  these  tumours  ;  and  the  occurrence  of  instances  in  which 
the  whole  musculature  is  converted  into  a  dense  mass  of  small  tumours, 
to  which  I  have  previously  called  attention,  points  to  the  same  conclusion. 

Of  like  import  is  the  finding  of  uterine  myomata  concomitant  with 
similar  tumours  in  the  ovary,  broad  ligament,  round  ligament,  tube, 
vagina,  and  in  other  situations  adjacent  to  the  uterus,  of  which  many 
examples  have  been  recorded. 

Thus,  Neill  has  met  with  a  case  in  which  myomata  coexisted  in  the 
uterus,  broad  ligaments,  and  ovaries  ;  while  Virchow  long  ago  reported 
an  instance  in  which  the  uterus,  ovary  and  vagina  were  concurrently 
affected. 

Epithelioma  (vel  Carcinoma). — In  like  manner  with  the  foregoing,  I 
know  of  many  instances  in  which  primary  malignant  epithelial  tumours 
of  the  uterus,  have  been  found  in  association  with  gross  local  develop- 
mental irregularities. 

Thus,  examples  of  the  concurrence  of  cancer  of  the  cervix  with  the 
various  forms  of  uterine  duplicity,  have  been  recorded  by  Czerwenka,1 
Rossa,2  Pollosson,3  Huber,4  Biehl,5  Zweifel,6  Hasse,7  Janvrin,  Orthmann, 
Alexander,  Wertheim,  Penrose,  Vineburg  and  others.  In  cases  by 
Czerwenka  and  Jackson,  both  cancer  and  myomata  were  associated 
concurrently  with  uterine  developmental  defects. 

Instances  of  cancer  of  the  unicorn  uterus  have  been  reported  by 
Heinricius  and  Josephson.  In  a  patient  who  died  of  cancer  of  the  colon, 
Mackenzie  found  a  myomatous  tumour  of  the  one-horned  uterus. 

In  a  case  of  vaginal  atresia,  Sandheimer  met  with  cancer  of  the  corpus 
uteri ;  and  Neugebauer  has  seen  uterine  cancer,  in  a  pseudo-hermaphrodite 
with  hypertrophy  of  the  clitoris. 

The  concurrence  of  vaginal  cancer  and  uterine  myomata,  has  been 
noted  by  Warder.  In  a  patient  with  cancer  of  the  uterus,  Amann  found 
double  ureters  on  the  left  side. 

I  have  elsewhere  referred  in  some  detail,  to  the  association  of  uterine 
cancer  with  other  uterine,  ovarian,  and  pelvic  tumours,  including 
dermoids. 

These  items  show,  that  there  is  a  certain  connexion  between  develop- 
mental irregularities  and  cancer  formation. 

1  Double   uterus   and   vagina,  cancer  of  left   portio,   two  myomata  of  left  corpus 
•  A  Gyn.,  1900,  No.  7). 

Jterus  bicomis,  atresia  vaginae,  absence   of  left   kidney   and   ureter,    cancer   of 
cervix  (Cent.  {.  Oyn.,  1894,  No.  18). 

Bifid  uterus,  cancer  of  cervix  (Lyon  Mid.,  1899,  t.  xc.,  p.  125). 

Uterus  didelphys,  cancer  of  one  cervix  (Arch.  f.  path.  Anat.,  1887,  Bd.  cviii.,  S/124). 
Uterus  bicornis  unicollis  with  cancer  of  cervix — two  cases  (Mittheil.  d.   Vereins 
d.  Aerzte,  etc.,  1894,  No.  4,  p.  103). 

Uterus  duplex,  cancer  of  cervix  (Cent.  f.  Gyn.,  1888,  p.  47). 

Uterus  bicornis,  defective  development'of  right  kidney,  cancer  of  cervix  (Deutsche 
Klin.,  1860,  vol.  xii.,  p.  329). 


THE  GENESIS  OF  MALIGNANT  TUMOURS  165 

Sarcoma. — In  a  few  cases,  uterine  sarcomata  have  also  been  found  in 
association  with  various  developmental  defects ;  thus,  Howe x  and 
Czerwenka  have  seen  sarcoma  concomitant  with  double  uterus,  and 
Briesky  the  same  disease  with  "  septum  vaginae  retro-hymenale." 
Flatau,  in  each  horn  of  uterus  introrsum  arcuatus,  found  a  myomatous 
tumour,  from  one  of  which  sarcomatous  disease  had  originated.  Braxton 
Hicks  had  described  a  case  of  congenital  absence  of  the  uterus,  tubes,  and 
ovaries,  in  which  a  large  cystic  myxo-sarcoma  occupied  the  place  of  the 
absent  uterus. 

These  examples  suffice  to  show,  that  this  form  of  malignant  uterine 
disease  may  also  be  associated  with  gross  developmental  irregularity. 

This  concludes  the  evidence  at  present  available,  as  to  the  association 
of  the  origin  of  uterine  tumours  with  pre-natal  developmental  irregu- 
larities ;  but,  no  doubt,  when  attention  has  once  been  directed  to  this 
matter,  additions  will  be  made  to  the  weighty  items  above  adduced. 
However  this  may  be,  in  their  ensemble,  these  facts  of  themselves  suffice 
to  prove  the  correctness  of  our  hypothesis. 


Mammary  Tumours  and  Developmental  Irregularity. 

The  ordinary  anatomical  description  of  the  female  mammary  gland, 
as  a  flattened  disc-shaped  mass,  is  certainly  very  misleading.  The  truth 
is  that  the  mamma,  like  the  lachrymal  and  salivary  glands,  is  normally  a 
very  imperfectly  integrated  organ,  for  its  constituent  lobules,  instead 
of  being  compacted  together  in  a  small  space,  are  generally  widely 
diffused  ;  moreover,  in  the  corpus  mammce,  its  vicinity,  and  in  the  axilla, 
detached  glandular  structures  are  of  common  occurrence.  It  seems 
certain,  as  I  have  elsewhere  shown,2  that  most  of  these  redundant 
glandular  structures  are  derived  by  sequestration  from  the  matrix  of  the 
evolving  gland,  during  pre-natal  life.  Besides  these  anomalies,  we  know 
from  studying  the  embryology  of  the  mamma,  that  the  ducts  of  some  of 
its  component  lobules,  instead  of  being  integrated  with  the  majority  of 
their  congeners,  are  nearly  always  left  behind  when  the  nipple  is  upraised  ; 
and  open  about  its  base,  rather  than  with  them  at  the  apex  of  the  nipple, 
where  they  are  known  as  the  glands  of  Montgomery,  which  really  are 
glandulce  lactiferce  aberrantes. 

It  has  been  shown  by  Schultze,  Kallius  and  Schmidt,  that — in  human 
beings,  as  in  polymastic  animals — the  first  mammary  rudiment  presents 
as  a  linear  thickening  of  the  epidermis,  which  extends — on  each  side — 
from  the  base  of  the  evolving  anterior  extremity  to  the  inguinal  region  : 
this  is  the  "  mammary  ridge,"  or  common  rudiment  of  the  mammary 
glands.  In  human  beings,  spindle-shaped  thickenings  appear  at 
intervals,  during  the  second  month  of  pre-natal  life,  in  the  course  of  each 
milchlinie.  After  a  time,  the  connecting  strands  usually  disappear  ;  and 
only  as  many  lenticular  thickenings  persist,  as  correspond  to  the  number 
of  mammae  normal  in  post-natal  life.  These  linear  ridges  at  first  occupy 

1  Boston  Medical  and  Surgical  Journal,  1876,  vol.  xcv.,  p.  224. 

2  "  Diseases  of  the  Breast,"  1894,  chap.  iv. 


166  THE  NATURAL  HISTORY  OF  CANCER 

a  dorsal  position ;  but  subsequently  they  migrate  towards  the  ventral 
surface.  It  is  easy  to  understand  how,  in  the  course  of  these  modifications 
and  migrations,  portions  of  the  matrix  may  be  detached  and  left,  in  the 
axilla,  or  in  other  positions,  where  they  subsequently  give  rise  to 
aberrant  glandular  structures.  Thus  there  are  several  ways  in  which 
mammary  glandular  "  rests "  may  originate.  In  the  axilla  and  its 
vicinity,  detached  glandular  structures  of  this  kind,  which  not  unfre- 
quently  secrete  milk  during  lactation,  are  by  no  means  rare,  as  I  have 
shown  in  my  book  on  "  Diseases  of  the  Breast,"  l  where  many  examples  of 
this  kind  are  cited. 

In  the  corpus  mammae  and  its  vicinity,  similar  mammary  glandular 
sequestra  have  also  been  noted.  "  True  adenoma  "  is  the  name  given  by 
some  pathologists  to  mammary  tumours,  structurally  exactly  like  a 
segment  of  the  breast  itself  ;  but  not  in  organic  continuity  with  the 
mamma  and  its  ducts.  Tumours  of  this  kind  are  not  particularly  rare  ; 
and,  it  is  such  as  these,  that  occasionally  secrete  milk  (so-called  "  milk- 
secreting  adenoma,"  some  galactoceles  etc.).  A  thorough  examination 
of  this  subject,  in  connexion  with  my  investigations  relating  to  super- 
numerary mammary  sequestrations,  has  convinced  me,  that,  in  these 
cases,  we  have  to  do  with  overgrown  mammary  ''  rests,"  rather  than 
with  true  neoplasms.  Such  is  the  nature  of  two  remarkable  cases  of 
"  milk- secreting  adenomata,"  reported  by  Birkett ;  2  of  a  case  of  "true 
adenoma,"  described  by  D'Arcy  Power ; 3  and  of  a  milk-secreting  cyst, 
found  in  a  cystic  sarcoma  by  Billroth.4  Examples  of  tumour-like  swell- 
ings of  similar  origin,  in  other  parts  of  the  breast  and  its  vicinity,  have 
been  recorded  by  Oilier,  Labbe  and  Coyne,  Eve,  Liicke,  Forbes,  Cameron, 
and  myself  (from  a  specimen  in  University  College  Museum),  as  detailed 
in  my  book  on  "Diseases  of  the  Breast."5  It  seems  certain  that  the 
germs  of  these  redundant  mammary  glandular  structures,  must  have 
been  detached  from  the  matrix  of  the  evolving  gland,  in  early  pre-natal 
life. 

That  tumours — identical  in  structure  with  mammary  tumours — 
frequently  arise  from  "  rests  "  of  this  kind,  I  have  clearly  proved  in  my 
above-mentioned  work  on  "  Diseases  of  the  Breast."  In  fact,  of  the 
mammary  tumours  specially  examined  by  me  ad  hoc,  I  was  able  to  deter- 
mine that  14  per  cent,  of  the  nbro-adenomata,  and  9-8  per  cent,  of  the 
malignant  epithelial  tumours,  thus  originated ; 6  as  well  as  to  indicate 
several  instances  of  adeno-sarcomatous  and  adeno-myxomatous  tumours 
similarly  derived.  This  being  so,  it  seems  not  unreasonable  to  assume, 
that  the  germs  of  most  mammary  tumours  are  similarly  conditioned. 

It  accords  with  this,  that  other  remarkable  instances  of  heterotopia 
are  also  met  with  in  the  breast,  and  its  tumours. 

Thus  Rindfleisch,   Hacker,   Astley  Cooper  and  others,   have  found 

1  Chap,  iv.,  §§  4  and  5. 

2  Guy's  Hospital  Reports,  1855. 

3  Transactions  of  the  Pathological  Society,  London,  1885,  vol.  xxxvi.,  p.  411. 

4  Arch.  f.  path.  Anat.,  Bd.  xviii.,  S.  68. 

5  Pp.  63,  73,  and  462. 

6  For  recent  cases  of  this  kind,  vide  Savariaud  (BuU.  et  Mem.  Soc.  Anat.,  Paris,  1906, 
No.  6,  p.  476);  and  Graham  (Journal of  American  Medical  Association,  August  27,  1898), 
with  references  to  other  cases  of  this  kind  in  the  axilla. 


THE  GENESIS  OF  MALIGNANT  TUMOURS  167 

cartilaginous,  ossiform,  calcareous,  and  even  truly  osseous  structures, 
embedded  in  the  otherwise  normal  mamma,  usually  in  the  form  of  localized 
deposits  ;  but  Bryk,  Berard,  and  others,  have  met  with  diffuse  calcifica- 
tion, sometimes  in  combination  with  true  ossification. 

The  most  feasible  explanation  of  the  presence  of  these  anomalous 
formations  in  this  situation,  is  that  which  ascribes  their  origin  to  the 
sequestration  of  sclerogenous  elements  from  the  matrix  of  the  evolving 
thoracic  skeleton,  in  early  pre-natal  life  ;  and  their  subsequent  inclusion 
in  the  nascent  mammary  rudiment. 

It  seems  certain  that  the  various  chondromatous  and  osteomatous 
tumours,  primarily  arising  in  the  breast,  of  which  Leser,1  Hacker,  Pied, 
Lange,  Cruveilhier,  Cambria,  Stefanini,  Astley  Cooper,  Nelaton,  Warren, 
Wagner,  J.  Muller,  Morgagni  and  others,  have  reported  examples,  origi- 
nated from  aberrant  elements  of  this  kind. 

These  cartilaginous  and  ossifying  tumours,  as  I  have  previously 
pointed  out,  are  especially  common  in  the  mammae  of  the  female  dogs  ; 
in  which  they  are  often  associated  with  various  forms  of  malignant 
disease,  as  well  as  with  adenoma. 

In  humanity  "  mixed  tumours  "  of  this  kind  also  occur  ;  thus,  instances 
of  malignant  epithelial  tumours  concomitant  with  heterotopic  cartila- 
ginous and  osseous  structures,  have  been  reported  by  Coen,  Gross,  Hacker, 
Warren,  Heurtaux,  Wagner,  Busch  etc.  In  such  cases,  the  cancerous 
disease  probably  originated  from  glandular  structures,  displaced  from 
their  proper  connexions  by  entanglement  with  skeletal  sequestra  :  in 
Heurtaux's  case,  glandular  cancer  was  concomitant  with  ossifying  and 
chondrifying  sarcoma,  as  was  proved  by  the.  nature  of  the  secondary  , 
growths,  which  reproduced  the  peculiarities  of  the  primary  tumour.  Y  ' 

In  mammary  sarcomata  similar  foreign  elements  have  been  found 
by  Arnold,  Stilling,  C.  A.  Morton,  Routier,  Bowlby,  Pilliet,  Coats,  Battle, 
Lecene,  Hueter,  Durham  etc.  ;  small  calcareous  concretions  in  these 
tumours  have  been  seen  by  Olivier,  Neugebauer,  Ackermann  etc.  ; 
while,  in  Dubar  and  Clarke's  cases,  extensive  areas  of  the  neoplasm  were 
calcified. 

In  myxomatous  tumours,  similar  structures  have  been  noted  by 
BiUroth,  Leloir  etc. 

Gross  and  Durham,  in  fibro-adenomata,  found  similar  conditions 
(osseous  heterotopia)  ;  and  in  both  these  cases  sarcoma  subsequently 
supervened. 

A  remarkable  instance  of  a  different  kind  of  heterotopia,  has  been 
published  by  Billroth  :  in  a  small  round-celled  sarcomatous  growth 
removed  from  the  breast  of  a  girl  aged  sixteen,  he  found  numerous 
transversly  striated,  spindle-shaped  muscle  cells.  In  this  case,  it  seems 
probable  that  the  foreign  elements  were  derived  by  sequestration  from 
adjacent  transversely  striped  muscle  matrix,  detached  during  the 
changes  incidental  to  mammary  development,  in  early  pre-natal  life. 

In  like  manner,  dermoid  cysts  of  the  breast  no  doubt  arise,  by  seques- 
tration from  the  epiblastic  rudiment  of  the  evolving  gland  in  pre-natal 

1  For  details  and  bibliographical  references  to  cases  cited  in  this  section,  the  reader 
is  referred  to  my  book  on  "  Diseases  of  the  Breast." 


168  THE  NATURAL  HISTORY  OF  CANCER 

life,  of  which  examples  have  been  recorded  by  Rocher,  D'Or,  Hermann, 
Ribbert,  Reverdin  and  Mayor,  Van  der  Byl,  Albers,  Velpeau,  Gerdy, 
Guyot  and  others.  All  of  these  were  simple  epidermoidal  cysts,  with 
the  exception  of  Albers',  which  was  also  piliferous. 

In  several  instances  heterotopic  epidermoidal  formations,  have  been 
found  comprised  in  fibro-cystic  and  fibro  -  adenomatous  tumours 
(J.  Griffiths,  Borst,  Haeckel  etc.)  of  this  part. 

A  similar  concomitancy  of  dermoid  cyst,  with  adeno- cystic  sarcoma  of 
the  mamma,  has  been  seen  by  J.  Miiller  ;  and  in  cystic  sarcomatous 
tumours  of  this  part,  Borchmeyer,  B.  Schmidt,  Model,  Grohe,  Kiirsteiner, 
Ribbert,  Lecene,  Wilms  and  others,  have  met  with  epidermoidal  "  rests," 
hornifying  pearls  etc. 

It  is  to  epidermoidal  "  rests  "  such  as  the  foregoing,  that  we  must  look 
for  the  germs  of  the  rare  primary  melanotic  tumours  of  the  mamma,  of 
which  examples  have  been  studied  by  Cornil,  Billroth,  and  Gurlt. 

Thus  for  mammary,  as  for  uterine  tumours,  I  have  shown  that  a  con- 
siderable proportion  arise  from  aberrant  structural  elements,  detached 
from  their  normal  connexions  during  pre-natal  life,  owing  to  develop- 
mental irregularity  ;  and  these  tumours  all  bear  the  impress  of  their  origin, 
visibly  stamped  in  their  structure.  This  being  so,  it  may  be  inferred  that 
even  tumours  in  which  this  impress  cannot  be  detected,  nevertheless, 
have  their  origin  similarly  conditioned. 

Moreover,  there  are  just  as  good  reasons  for  believing,  that  what  is 
true  for  the  origin  of  uterine  and  mammary  tumours,  is  equally  valid 
for  the  origin  of  all  tumours. 


CHAPTER  VIII 
THE  EXPERIMENTAL  STUDY  OF  CANCER  GENESIS 

IT  must  be  confessed  that  the  results  of  the  many  attempts  which  have 
been  made  to  produce  histioid  tumours  experimentally — whether  by 
implanting  normal  tissue  elements,  or  those  derived  from  tumours,  or 
by  injecting  the  cultures  of  various  so-called  "  cancer  microbes  " — have, 
on  the  whole,  been  disappointing. 

So  far  as  malignant  tumours  are  concerned,  the  results  have  hitherto 
been  entirely  negative,  although  some  pathologists  claim  to  have  met 
with  positive  results,  of  which  more  anon. 


Experiments  with  Normal  Tissue  Elements. 

Epidermoidal  tissues  are  remarkable  above  all  others  for  their  great 
regenerative  power,  and  for  their  tenacious  vitality  ;  while  the  facility 
with  which  even  large  pieces  of  skin  may  be  transplanted,  is  well  known 
to  surgeons,  who  have  practised  the  plastic  methods  of  Thiersch, 
Reverdin,  Oilier  etc. 

Even  epidermoidal  scrapings,  the  shavings  of  warts,  dried  bits  of 
cuticle  separated  by  burns,1  the  cuticle  raised  by  blistering  etc.,  have  been 
successfully  employed  for  healing  ulcerated  surfaces,  by  grafting  them 
thereon.  Recent  experiments  as  to  the  limit  of  the  vitality  of  the  skin 
after  its  removal  from  the  body  etc.,  have  greatly  altered  old  ideas  as  to 
the  possibilities  in  this  direction.  Thus,  pieces  of  skin  from  amputated 
limbs  have  been  found  to  retain  their  vitality,  for  thirty-six  hours  after 
their  removal  from  the  body  (Brewer)  ;  and,  when  suitable  temperature 
and  other  conditions  have  been  maintained,  for  much  longer  periods — 
e.g.,  for  ninety-six  hours  (Marten),  for  several  weeks  (Wentscher),  or  even 
for  several  months  (Ljunggren). 

Of  all  the  tissues  of  the  body,  the  epithelial  ones  have,  on  the  whole, 
departed  less  from  the  primordial  cellular  type  than  any  others,  and  their 
constituent  elements  ("  labile  ")  are  constantly  proliferating  during  the 
whole  life  of  the  individual ;  hence  their  cells  still  retain  their  primitive 
powers  of  growth  and  reproduction  in  higher  degree  than  any  others. 
Thus  may  we  account  for  their  great  regenerative  power,  their  remarkable 
vital  tenacity  ;  and  to  this  source  may  also  be  ascribed  their  undue 
proclivity  to  malignant  and  non-malignant  tumour  formation. 

1  Lusk  found  that  such  separated  cuticle  retained  its  vitality,  and  grew  when  grafted, 
even  five  weeks  after  its  separation  (New  York  Medical  Journal,  December  21,  1895, 
p.  799). 

169 


170  THE  NATURAL  HISTORY  OF  CANCER 

It  has  been  observed  of  many  tissue  transplantations,  that  they 
have  succeeded  much  better  when  pre-natal  grafts  were  employed,  than 
with  grafts  derived  from  the  post-natal  period.{- '"  ^~^^^^J^^^ 

With  regard  to  epidermoidal  transplant ation7  it  is  doubtful  whether 
any  such  distinction  is  valid  ;  at  any  rate,  some  of  the  most  successful 
results  have  been  attained  with  post-natal  elements. 

When  pieces  or  small  fragments  of  epithelial  tissues,  derived  from  early 
pre-natal  life,  are  transplanted  or  injected  into  adult  animals,  most  of 
these  grafts  grow  and  even  undergo  a  certain  amount  of  differentiation, 
similar  to  what  they  would  normally  have  undergone,  had  they  retained 
their  normal  connexions ;  thus,  in  grafts  of  this  kind,  transplanted 
epithelial  cells  have  even  been  known  to  assume  the  glandular  form  etc. 
After  a  time,  however,  their  constituent  cells  generally  cease  to  grow, 
and  are  eventually  absorbed. .  In  some  instances,  most  of  the  grafts 
degenerated  from  the  start,  such  growth  as  subsequently  supervened 
taking  place  from  the  surviving  elements  (Barfurth,  Fere,  Loeb,  Lubarsch, 
Levin,  Masse  etc.). 

In  a  few  instances,  it  appears  that  epidermoidal  cysts  have  resulted 
from  experiments  of  this  kind  ;  but,  as  to  the  permanence  of  such 
artificially  produced  new  formations,  there  is  need  of  further  evidence^ 
Certainly,  no  other  kind  of  non-malignant  epithelial  tumour  has  ever  been 
produced  in  this  way  ;  and,  above  all,  nothing  like  cancer  has  ever  resulted. 

By  implanting  into  the  peritoneal  cavity  of  young  white  rats,  bits  of 
skin  and  parts  of  limbs  of  newly-born  rats,  Masse  *  succeeded  in  artificially 
producing  epidermoidal-lined  cysts,  containing  hairs,  epidermoidal  debris 
and  cholesterine  :  such  were  the  conditions  found,  when  the  animals  were 
killed,  two  and  a  half  months  after  the  initial  operations.  In  like  manner 
he  succeeded  by  subcutaneous  grafts,  in  artificially  producing  subcu- 
taneous "  pearly  "  tumours. 

Levin,2  by  transplanting  small  pieces  of  foetal  skin  into  the  peritoneal 
cavity  of  rabbits,  in  two  cases  found  that  one  or  more  epidermoidal 
"  pearly  "  tumours  resulted. 

Nichols,3  having  transplanted  epidermis  from  a  foetal  rabbit,  into  the 
subcutaneous  tissue  of  the  ear  of  its  mother,  saw  a  "  pearly  "  tumour 
form  from  the  graft,  which  grew  more  quickly  than  when  post-natal 
epidermis  was  used  for  the  experiment. 

Similar  experiments,  with  post-natal  epidermoidal  tissues,  have  given 
almost  identical  results  (Kaufmann,  Ribbert,  Schweniger  etc.). 

Kaufmann4  made  numerous  experiments  to  ascertain  the  fate  of 
embedded  skin,  employing  chiefly  the  combs  and  wattles  of  fowls,  which 
are  very  vascular  tissues.  Islands  of  surface  skin  were  circumscribed  by 
continuous  incision  ;  flaps  were  raised  on  each  side  and  united  by  sutures 
over  each  cutaneous  island,  which  still  maintained  its  normal  relations 
with  its  connective-tissue  substratum. 

Kaufmann  found  that  the  rate  of  increase  of  the  embedded  epidermis 

1  Bull.  gen.  de  therap.  Med.  et  Chir.,  1885,  t.  cviii.,  p.  337. 

2  Journal  of  Medical  Research,  1901,  vol.  vi.,  p.  145. 

3  Third  Report  of  the  Croft  Cancer  Committee  of  Harvard  Medical  School,    1905, 
p.  116. 

4  Arch.  f.  path.  Anat.,  Bd.  xcvii.,  S.  236. 


THE  EXPERIMENTAL  STUDY  OF  CANCER  GENESIS     171 

was  greatly  in  excess  of  the  normal,  the  grafts  curling  up  at  their  margins 
and  forming  cyst-like  structures,  resembling  the  simpler  kinds  of  dermoid    V 
cyst.     This  increase,  in  some  cases,  continued  as  long  as  210  days,  when  a 
stationary  condition  was  attained. 

In  connexion  with  the  increased  rate  of  growth  here  noticed,  it  is  of 
interest  to  recall  John  Hunter's  experiment,  of  transplanting  the  cock's 
spur  to  its  comb  ;  where  it  grew  to  a  size  much  in  excess  of  the  normal, 
apparently  owing  to  the  increased  vascularity  of  its  new  substratum. 

Ribbert l  cut  out  skin  flaps,  and  while  each  was  still  connected  with 
its  natural  basis  by  a  narrow  pedicle,  it  was  introduced  into  the  abdominal 
cavity,  where  each  quickly  adhered  by  its  connective-tissue  surface  to 
the  peritoneum,  enclosing  the  epidermis  in  a  cyst-like  cavity.  When 
these  inclusions  were  examined  after  a  sufficient  lapse  of  time,  they  were 
found  to  have  been  converted  into  epidermoidal- lined  cysts,  with  hairs 
growing  from  their  walls,  which  contained  epidermoidal  debris  etc. 

Marnoch,2  however,  repeating  experiments  of  this  kind  on  guinea- 
pigs  and  rabbits,  found  in  every  case  that  the  embedded  tissue  was 
quickly  absorbed. 

The  possibility  of  the  experimental  production  of  epidermoidal  cysts, 
and  "  pearly  "  tumours,  is  confirmed  by  the  fact  that  tumours  of  this 
kind  have  often  formed  after  certain  traumata,  in  consequence  of  portions  X 
of  epidermis  being  displaced  from  their  normal  connexions,  and  implanted 
amidst  other  tissues. 

Most  instances  of  this  kind  have  been  met  with  in  the  hand  (especially 
the  palmar  surface  of  the  digits)  and  iris  ;  but  also  in  other  parts  (vagina, 
cornea,  thorax,  thigh  etc.). 

These  implantation  cysts  usually  contain  turbid  or  milky  fluid,  with 
pearly  white,  laminar  epidermoidal  tissue,  within  a  fibrous  pseudo- 
capsule  :  the  polymorphic,  epidermoidal  cells  are  arranged  in  successive 
layers,  the  deeper  ones  of  cubical  or  columnar  form,  merging  gradually 
into  hornified  cells,  as  described  by  Polaillon  (1884).  In  exceptional 
cases  fragments  of  cutis  vera  are  implanted,  which  may  sometimes 
maintain  a  connexion  with  the  surface  skin  :  in  the  walls  of  such  cysts, 
papillae,  glands,  and  even  hairs,  have  been  seen.  Instances  have  also  been 
reported  in  which  the  foreign  body  causing  the  implantation,  has  been 
found  in  the  tumour  ;  thus,  Mr.  C.  A.  Morton,3  met  with  a  thorn  in  the 
midst  of  the  cornified,  laminated  matter,  from  a  tumour  of  this  kind  in 
the  thigh,  which  was  known  to  have  existed  for  nearly  thirty  years. 
Condon  4  has  reported  an  example  of  an  epidermoidal  cyst  of  the  anterior 
thoracic  wall,  secondary  to  fracture  of  the  adjacent  ribs.  In  bovine 
animals,  piliferous  subcutaneous  cysts  have  been  seen,  which  appeared 
to  have  resulted  from  skin  implantations,  caused  by  the  drovers  prodding 
the  animals  with  the  sharp  goad. 

The  traumatic  origin  of  implantation  cysts  of  the  iris  was  first  indicated 
by  Hulke  (1869),  who  ascertained  that  in  fifteen  out  of  nineteen  recorded 
cases,  some  form  of  penetrating  wound  had  preceded  the  appearance  of 

1  Deuteche  med.   Woch.,  1895,  Nos.  1,  2,  3,  and  4. 

2  Lancet,  1901,  vol.  ii.,  p.  6. 

3  Bristol  Medico-Chir.  Journal,  1894,  vol.  xii.,  p.  252. 

4  Journal  of  Pathology,  etc.,  1901,  vol.  vii.,  p.  368. 


172  THE  NATURAL  HISTORY  OF  CANCER 

the  tumours,  whose  epidermoidal  structure  he  determined.  The  germs 
whence  these  cysts  arise  are  displaced  bits  of  corneal,  conjunctival,  or 
even  eyelid  cuticle.  In  several  cases  they  have  been  found  associated 
with  a  displaced  eyelash,  carried  into  the  eye  by  the  wounding  agent. 
The  correctness  of  this  aetiology  has  been  experimentally  proved  by 
Masse  (1881),  who  caused  tumours  of  this  kind  by  grafting  bits  of 
conjunctiva  into  the  iris  of  rabbits  etc. 

1 1  have  previously  referred  to  the  artificial  production  of  uterine  cysts, 
by  the  implantation  of  grafts  of  uterine  mucosa. 

A  sensation  was  caused  among  pathologists  some  years  ago,  when 
Lack l  claimed  to  have  succeeded  in  experimentally  producing  cancer,  by 
intra-abdominal  auto-implantation  in  a  rabbit. 

Having  opened  the  peritoneal  sac  and  bisected  each  ovary,  the  raw 
surfaces  of  the  latter  were  freely  scraped  with  a  sharp  knife,  the  detached 
juicy  and  parenchymatous  ovarian  products  being  diffused  throughout 
the  peritoneal  cavity.  The  abdominal  wound  was  then  closed,  and  the 
animal  recovered.  It  remained  well  for  a  year,  but  then  got  thin  and 
weak ;  and  was  killed  in  this  condition  fourteen  months  after  the 
initiation  of  the  experiment.  At  the  post-mortem  examination,  the 
peritoneum  was  found  studded  with  tumour-like  formations,  as  well  as 
the  liver,  diaphragm,  mediastinum  and  uterus.  Histologically  examined, 
sections  of  these  growths  presented  the  appearance  of  alveolar  spaces, 
lined  by  one  or  more  layers  of  columnar  epithelial  cells.  Other  patho- 
logists who  have  repeated  this  experiment,  and  various  modifications  of 
it,  have  failed  to  reproduce  similar  morbid  appearances  :  their  grafts 
etc.,  after  a  time,  completely  disappeared  (Levin,  Basso,  Shattock, 
Nichols,  Enderlin,  Ribbert  etc.). 

I  have  previously  referred  to  possible  explanations  as  to  Lack's 
success  ;  which,  in  the  absence  of  corroboration,  cannot  be  accepted  as 
an  example  of  the  experimental  production  of  cancer. 

It  accords  with  this,  that  experiments  made  on  other  parts  of  the 
body  with  the  same  object  in  view,  have  yielded  only  negative  results. 
Thus  the  attempts  of  Gilbert  and  Roger  to  produce  cancer  of  the  mamma, 
in  old  bitches,  by  subjecting  the  part  to  various  forms  of  mechanical  irrita- 
tion, completely  failed  ;  and  Cazin,  by  rubbing  soot  into  irritated  parts, 
was  equally  unsuccessful,  although  the  soot  particles  were  taken  up  by  the 
local  cells,  as  is  known  to  be  the  case  in  that  form  of  cancer  of  the  scrotum 
called  "  chimney-sweep's  cancer." 

It  was  just  the  same  with  the  experiments  of  D'Arcy  Power,2  Pier- 
allini  and  Galeotti.  Lately  B.  Fischer  3  has  made  fresh  experiments  :  the 
tissues  of  the  rabbit's  ear  having  been  injected  with  a  mixture  of  olive  oil 
and  the  fat-staining  dye  "  Scharlach  B,"  the  cutaneous  epithelium  of  the 
part  was  in  this  way  separated  from  the  subjacent  tissues.  Soon  after- 
wards these  epidermoidal  cells  showed  mitoses  ;  they  thickened,  ingrowing 
processes  appeared,  which  penetrated  the  subjacent  parts  and  even 
perforated  the  cartilage  of  the  auricle,  while  epithelial  pearls  formed  etc. 
In  short,  in  all  of  these  experiments,  the  histological  appearances  of  the 

1  Journal  of  Pathology,  etc.,  1900,  vol.  vi.,  p.  154. 

2  Ibid.,  1896,  vol.  iii.,  p.  124  ;  also  1897,  vol.  iv.,  p.  69. 

3  Miinch.  med.  Woch.,  1906,  Bd.  liii.,  S.  2042. 


THE  EXPERIMENTAL  STUDY  OF  CANCER  GENESIS      173 

damaged  parts  were  very  similar  to  those  seen  in  malignant  epithelial 
tumours. 

Under  these  circumstances,  it  is  impossible  to  admit  the  validity  of 
the  claims  of  Hemmeter,1  Maniscalio,2  Fiitterer 3  etc.,  to  have  caused 
"  adeno-carcinoma  "  of  the  stomach  in  various  animals  by  irritating 
artificially-produced  ulcers  ;  for  these  claims  rest  solely  on  the  local 
histological  appearances,  which  in  the  absence  of  other  signs  of  malignancy, 
are  by  no  means  conclusive. 

Some  pathologists,  experimenting  with  tissue  implantations,  have 
reported  that  grafts  into  the  ovaries  grew  better  than  those  in  other 
localities.  Here  Loeb's 4  interesting  observations,  as  to  the  growth  of 
epidermoidal  cells  in  blood-serum  and  in  agar  must  be  recalled.  In  this 
strange  environment,  the  epithelial  cells  grew  and  multiplied  with  great 
freedom — quite  independently  of  any  connective-tissue  substratum — 
reproducing  most  of  the  histological  appearances  of  epithelioma,  as  above 
detailed. 

Epithelium  in  process  of  regeneration,  wherever  found,  manifests 
similar  changes  ;  and  Loeb 5  has  specially  called  attention  to  certain 
resemblances  between  the  histological  appearances  of  epithelial  healing 
and  epithelial  cancer. 

Lately  the  interesting  discovery  has  been  made  that,  by  treating 
proliferating  cells  with  various  poisons  and  chemical  reagents  (quinine, 
chloral,  cocaine,  antipyrin  etc.),  analogous  irregularities  in  their  mitoses 
and  mode  of  growth  can  be  artificially  produced,  even  when  quite  dilute 
solutions  are  used. 

It  has  also  been  shown  by  B.  Moore  that,  even  the  reducing  division, 
supposed  to  be  characteristic  of  reproductive  cells,  which  had  hitherto 
only  been  met  with — outside  this  sphere — in  malignant  tumours,  can 
also  be  produced  artificially,  as  well  as  other  karyokinetic  irregularities, 
by  treating  proliferating  cells  with  alkaline  solutions  of  a  certain  strength. 

These  results  suggest  the  possibility,  that  the  similar  irregularities  in 
the  proliferation  of  the  cells  of  malignant  tumours,  may  be  due  to  the 
presence  of  some  unknown  bio-chemical  agency. 

Here  attention  may  be  called  to  the  fact,  long  well  known  to  human 
pathologists,  that  in  most  chronic  hyperplastic  processes  of  epithelial- 
covered  parts,  quite  analogous  morphological  changes  commonly  occur. 
Conditions  of  this  kind  have  been  specially  studied  by  Wyss,6  Fried- 
lander,7  Councilman8  and  others 

Waldeyer,  from  the  histological  standpoint,  having  proposed  for 
cancer  the  very  short-sighted  definition  of  "  atypical  epithelial  prolifera- 
tion," was  soon  made  conscious  of  the  serious  inadequacy  of  such  a  con- 
ception, by  the  above-mentioned  histological  researches,  which  showed 
that  "  atypical  "  epithelial  ingrowths  were  common  enough,  in  many 
chronic  hyperplastic  processes  affecting  epithelial-covered  surfaces. 

American  Journal  of  Medical  Science,  April,  1903.         3  Rif.  Med.,  April  1, 1905. 

"  liber  die  Aetiologie  des  Carcinoms,"  etc.,  1903. 

Journal  of  Medical  Besearch,  1902,  vol.  viii.,  p.  109. 

Arch.  f.  Entwickelungs-rnech.,  etc.,  1898,  vi.,  S.  297. 

Arch.  f.  path.  Anat.,  Bd.  Ixix.,  S.  24. 

"  Ueber  Epithelwucherung  und  Krebs."     Strassburg,  1877. 

Johns  Hopkins  Hospital  Bulletin,  No.  2,  1890. 


174  THE  NATURAL  HISTORY  OF  CANCER 

One  of  the  best  examples  of  this  is  furnished  by  the  so-called 
"  erosions  "  of  the  portio  vaginalis  uteri,  wherein  newly  formed  structures 
abound,  very  like  cancer  structures.  These  consist  of  ingrowths  of  the 
local  epithelium,  into  the  subjacent  granulation  tissue,  which  is  thus 
interpenetrated  by  branching,  anastomosing,  ingrowing  epithelial 
processes  and  networks.  These  are  usually  hollow,  but  not  infrequently 
also  quite  solid  cellular  processes  and  "  nests,"  may  be  formed.  Thus 
a  perfect  histological  counterpart  of  the  structures  commonly  met  with 
in  epithelial  cancer  of  this  part  may  be  reproduced  ;  and  yet  the  con- 
dition is  quite  innocent,  for  it  lacks  the  quality  of  malignancy.  This 
quasi-cancerous  process  is  only  arrested  when  the  dense  connective- 
tissue  substratum  is  reached.  It  is  thus  evident,  that  the  epithelial 
proliferation  of  cancer  is  not  without  counterparts,  in  various  other 
morbid  processes. 

The  knowledge  of  the  foregoing  facts  enables  us  to  understand  how 
quasi-malignant  tumours,  comprising  proliferous  epithelial  elements, 
may  be  caused  by  many  various  extrinsic  agents,  e.g.,  traumatic, 
microbic,  chemical  etc.  Thus,  cases  of  "  blastomycetic  dermatitis " 
have  been  described,  in  which  the  gross  and  microscopical  features  of 
the  lesions,  were  very  similar  to  those  of  cutaneous  cancer  (Gilchrist, 
Stokes,  Owens,  Hyde,  Hektoen  etc.)  ;  while  infectious  quasi-sarcomatous 
tumours,  similarly  derived,  have  been  met  with  in  men  and  animals 
(Busse,  Curtis,  Sanfelice  1  etc.)  ;  and  yet  the  disease  is  not  malignant. 
In  this  category  the  "  infective  epitheh'oses  "  of  Borrel  may  also  be  com- 
prised ;  and  I  have  no  doubt  that  "  Jensen's  tumour  "  of  mice,  and  Loeb's 
"  adeno-sarcoma  "  of  the  neck  of  white  rats,  are  of  the  same  nature. 

From  a  consideration  of  the  ensemble  of  the  foregoing  items,  it  may  be 
inferred  that  the  unknown  agent  which  causes  malignant  proliferation, 
is  not  specific  ;  but  rather  that  any  kind  of  stimulus  capable  of  exciting 
the  local  cells  to  undue  proliferative  activity  may  suffice.  And,  since  the 
ontological  history  shows  that  for  the  requirements  of  physiological  life, 
intrinsic  stimuli  are  by  far  the  more  effective  ;  so  it  is  likewise  probable 
that  under  pathological  conditions  tending  to  tumour  formation,  the 
same  kind  of  stimuli  prevail — such  as  serve  as  nuclear  pabulum  probably 
being  in  the  first  rank. 

With  regard  to  transplantation  experiments  with  normal  connective- 
tissue  structures,  whether  of  pre-  or  post-natal  origin,  the  general  outcome 
of  many  tentatives  has  been  that,  although  at  first  the  grafts  often  grew, 
yet,  after  a  time,  they  were  eventually  absorbed. 

In  these  experiments  the  maximum  of  success  has  been  with  foetal 
cartilage  (Zalm,  Leopold,  Birch-Hirschfeld  and  Garten). 

Zahn  2  injected  into  the  external  jugular  vein  of  rabbits,  foetal  cartilage 
from  the  same  animals  broken  up  in  liquor  amnii  ;  and  found,  when  he 
killed  and  examined  the  dead  animals  a  comparatively  short  time  after 
the  experiment,  numerous  cartilaginous  nodules  in  their  lungs — chiefly 
near  the  surface.  Similar  experiments  with  post-natal  cartilage  were 
entirely  negative. 

1  For  details  of  these  interesting  cases,  vide  Chapter  X. 

2  "  Sur  le  sort  des  tissues  implant  ej  dans  1'organisme  "  (G.  E.  Cong.  rued,  internal,  de 
Geneve,  1878,  p.  658). 


THE  EXPERIMENTAL  STUDY  OF  CANCER  GENESIS     175 

Leopold,1  continuing  Zahn's  line  of  research,  made  numerous  experi- 
ments as  to  the  effect  of  implanting  foetal  rabbit's  cartilage  into  the 
anterior  chamber  of  the  eye,  the  abdominal  cavity  and  the  external 
jugular  vein,  of  rabbits.  Of  these  the  most  successful  were  the  eye 
implantations,  some  of  the  grafts  increasing  even  to  the  extent  of  two  or 
three  hundred  times  their  original  size,  at  the  same  time  undergoing 
ossification,  and  maintaining  their  vitality  for  considerable  periods. 

Helmholz 2  caused  the  formation  of  numerous  small  cartilaginous 
nodules  in  the  rabbit's  ear,  by  scarifying  the  cartilage  of  the  same. 

By  injecting  a  mixture  of  finely  chopped-up  fowls'  embryos — in  normal 
saline  solution — into  dogs,  Ribbert 3  claims  to  have  produced,  in  a  few 
weeks'  time,  malignant  tumours  in  five  out  of  fourteen  dogs  experimented 
on.  To  these  claims  it  may  be  objected  that  the  lapse  of  time  was  not 
sufficient,  so  many  previous  experiments  having  shown  that  the  nodules 
which  formed  at  first  were  subsequently  completely  absorbed. 

Birch-Hirschfeld  and  Garten4  injected  into  the  liver  of  rabbits,  hens, 
goats,  frogs  and  salamanders,  an  emulsion  of  finely  divided,  mixed  foetal 
tissues,  variously  derived.  In  a  few  instances,  cartilaginous  formations  were 
found  in  the  liver  and  lungs  shortly  afterwards  ;  but,  they  were  all  event- 
ually absorbed — although,  in  the  case  of  a  salamander,  a  chondromatous 
formation  in  the  liver  still  persisted  forty-one  days  after  the  injection. 

In  like  manner,  Nichols 5  found  that  foetal  cartilage  from  a  female 
rabbit,  transplanted  into  the  maternal  subcutaneous  tissue,  gave  rise  to    ' 
a  considerable  nodular  growth,  in  which  there  was  ossification. 

Cohnheim  and  Maas6  introduced  into  the  jugular  vein  of  animals, 
portions  of  the  periosteum  of  the  tibia  of  post-natal  rabbits,  dogs  etc. 
These  lodged  in  the  lungs,  where  they  grew  for  a  time,  producing  cartilage 
and  bone  ;  but,  by  the  end  of  the  fifth  week  after  the  experiment,  all 
traces  of  them  had  completely  disappeared.  Similar  experiments  with 
various  foetal  tissues  by  Alessandri,  Lwoff  and  Levin — and  by  Ribbert, 
Lubarsch  and  Levin  with  post-natal  tissues — yielded  only  negative  results, 
the  grafts  being  invariably  disintegrated  and  absorbed. 

It  was,  however,  long  ago  shown  by  Oilier  7  that  detached  flaps  of 
periosteum  implanted  into  the  soft  parts,  gave  rise  to  bone  formation 
in  their  new  situations  ;  and,  even  the  juice  obtained  by  scraping  the  deep 
aspect  of  the  periosteum  led  to  bone  formation,  when  it  was  implanted 
subcutaneously. 

According  to  Knauer,8  McCone,9  Enderlin,  Ribbert,  and  others,  when 
entire  organs — such  as  the  ovary  and  thyroid — are  transplanted  into  the 
same  animal,  or  from  one  animal  to  another,  they  continue  to  survive  and 
to  perform  their  special  functions  in  their  new  surroundings.  Nichols,10 
and  Basso,11  however,  found  that  when  the  whole  ovary  or  half  of  it,  was 

Arch.  f.  path.  Anat.,  1881,  Bd.  Ixxxv.,  S.  283. 

Johns  Hopkins  Hospital  Bulletin,  September,  1907,  p.  269. 

"  Progressive  Medicine,"  1905,  vol.  ii.,  p.  158. 

Znegler's  Beitr.  z.  path.  Anat.,  1899,  Bd.  xxvi.,  S.  132. 

Third  Report  of  the  Harvard  Croft  Cancer  Committee,  1905,  p.  121. 

Arch.  }.  path.  Anat.,  Bd.  Ixx.,  S.  161. 

Journal  de  la  Physiologic  de  Vhomme  et  des  animaux,  1859,  t.  ii.,  pp.  1,  169,  and  468. 

8  Wien  klin.  Woch.,  December  7,  1899. 

9  American  Journal  of  Obstetrics,  etc.,  1899,  vol.  xl.,  p.  214. 

18  Op.  cit.  u  Monat-s.  f.  Geb.  u.  Oyn.,  Bd.  xxii.,  Heft  5. 


176  THE  NATURAL  HISTORY  OF  CANCER 

transplanted  into  the  subcutaneous  tissue  of  the  same  animal,  these 
grafts — after  a  sufficient  interval  of  time  (up  to  101  days) — were 
absorbed.  Schultz  l  showed  that  ovaries  transplanted  into  the  peri- 
toneal cavity  of  male  guinea-pigs,  dwindled  in  size  and  manifested  no 
signs  of  proliferative  activity,  at  the  end  of  eleven  days  after  implanta- 
tion ;  but  Hunter  long  ago  succeeded  in  grafting  the  testicle  of  a  cock 
into  the  belly  of  a  hen,  although  experiments  of  this  kind  generally  failed, 
and  the  grafted  organ  "  seldom  came  to  perfection." 

Shattock  and  Seligmann,  experimenting  with  incompletely  castrated 
cockerels,  found  that  where  minute  fragments  of  ruptured  testis — under- 
going maturation  and  gametogenous  processes — had  become  grafted  on 
the  liver,  intestine  etc.,  no  malignant  disease  ensued,  notwithstand- 
ing the  free  production  of  "  gametogenous "  tissue  in  the  grafts. 
Nichol's  implantations  of  testicular  substance  into  the  peritoneal  cavity, 
also  gave  similar  negative  results. 

By  transplanting  cross  sections  of  rabbit's  and  guinea-pig's  uterus, 
into  the  subcutaneous  tissue  of  the  abdomen  of  the  same  animal,  Nichols  2 
produced  cystic  formations,  which  were  in  some  instances  multiple.  The 
lining  of  these  cysts  resembled  that  of  the  uterine  mucosa.  The  trans- 
planted tissues  increased  and  maintained  their  capacity  for  growth  in 
most  cases,  as  evidenced  by  the  cellular  mitoses,  even  for  a  considerable 
time  after  the  experiments  ;  but,  in  no  case  did  there  result  a  new  for- 
mation having  the  least  resemblance  to  myoma,  or  to  any  kind  of 
malignant  tumour. 

The  possibility  of  transplanting  teeth  has  been  well  known,  ever  since 
the  time  of  Hunter,  who  not  only  transplanted  teeth,  from  one  part  of 
the  mouth  of  the  same  individual  to  another  part  of  the  mouth  ;  but  also, 
from  one  human  being  to  another  ;  from  one  animal  to  another,  and  from 
human  beings  to  animals.  In  the  Royal  College  of  Surgeons'  Museum, 
there  is  a  specimen  showing  the  successful  transplantation  by  Hunter, 
of  a  human  tooth  into  a  cock's  comb.3  The  tooth  grew  in  its  new  situa- 
tion, and  when  the  cock  died,  Hunter  injected  the  tooth  through  the 
bloodvessels  of  the  cock.  The  vitality  of  each  part  of  the  body,  seems  to 
have  a  certain  autonomy.  Another  curious  feature  of  transplanted  teeth 
is,  that  they  may  transmit  the  poison  of  syphilis.  Legros  and  Magitot  have 
shown,  that  the  dental  bulbs  may  also  be  grafted  on  to  the  neighbouring 
parts — three  out  of  sixteen  experiments  being  successful.  May  not  dis- 
placed bulbs  of  this  kind  be  the  germs  of  the  peculiar  warty  growths, 
described  by  Cock,  Salter  and  others,  as  sometimes  being  met  with  on  the 
gums,  and  on  the  adjacent  parts  of  the  hard  palate  ? 

Even  the  extremity  of  the  nose,  ear,  and  the  ends  of  fingers  and  toes — 
including  a  portion  of  the  bone — have  been  successfully  reunited  after 
recent  severance,  sometimes  after  the  lapse  of  several  hours. 

In  animals,  as  the  experiments  of  Bert  show,  the  transplantation  of 
parts  between  animals  of  the  same  species,  can  be  readily  effected  ;  thus, 
the  denuded  tails  and  feet  of  rats,  were  successfully  transplanted  beneath 
the  skin  of  other  rats,  as  also  detached  periosteum  and  teeth. 

1  Cent.  f.  allg.  Path.,  etc.,  1900,  Bd.  xi.,  S.  200. 

2  Op.  cit.,  p.  117.  3  No.  47,  Pathological  Series. 


THE  EXPERIMENTAL  STUDY  OF  CANCER  GENESIS     177 

In  none  of  the  foregoing  experiments,  except  in  the  case  of  epider- 
moidal  cyst  formation,  was  it  possible  to  produce  experimentally  anything 
that  could  be  properly  described  as  a  tumour  ;  although  Leopold's  results 
seem  to  indicate,  that  transplanted  foetal  cartilage  has  some  tendency  to 
evolve  in  this  direction. 


Experiments  with  Papillomatous  Tumours  etc. 

There  is  probably  some  basis  for  the  popular  belief,  as  to  the  occasional 
contagiousness  of  the  ordinary  cutaneous  wart  :  thus  Dr.  Payne  l  relates 
that,  after  having  used  his  thumbnail  to  effect  the  separation  of  warts  of 
this  kind,  three  similar  warts  developed  under  the  nail  of  this  thumb. 

Variot 2  has  succeeded  in  experimentally  transplanting  warts  of  this 
kind,  from  an  infant  to  a  man  :  the  same  author  has  also  met  with  an 
instance  of  concomitant  warts  on  the  hands  and  eyelids  of  a  child,  in 
which  it  seemed  probable  that  the  disease  had  been  transferred,  from  the 
former  to  the  latter  locality,  by  auto-inoculation. 

Billroth 3  has  noted  an  instance  of  the  auto-inoculability  of  these 
warts,  thus  he  says  :  "  I  saw  a  case  where  an  ordinary  wart  formed  on 
the  side  of  a  toe  ;  and,  on  the  part  of  the  neighbouring  toe  lying  in  contact 
with  it,  another  wart  formed." 

The  experiments  of  0.  Lanz  4  are  to  the  like  effect :  for,  having  finely 
chopped  up  some  warts  from  the  hand,  he  injected  the  product  into  the 
subcutaneous  tissue  of  the  same  person  ;  and  so  succeeded  in  artificially 
producing  a  fresh  crop.  Lanz  even  succeeded  in  implanting  thus  a  group 
of  warts,  in  the  form  of  the  capital  letter  J,  on  the  back  of  a  gardener's 
hand.  Similarly,  by  rubbing  a  healthy  digit  against  some  of  these 
warts,  the  disease  was  implanted  on  the  former. 

As  all  attempts  to  isolate  any  microbe  from  these  warts  failed,  Lanz 
concluded  that  the  epidermoidal  cells  of  the  growth  were  themselves  the 
infective  agent.  In  a  recurrent  wart  of  the  septum  nasi,  O'Kinealy5 
found  sporozoan  parasites ;  and  Beattie  has  demonstrated  a  similar 
condition  in  cases  of  aural  and  nasal  polypi. 

It  may,  however,  be  inferred,  from  the  fact  that  Leale6  and  others 
have  successfully  used  cut-up  warts,  as  grafts  for  promoting  the  healing 
of  ulcerated  cutaneous  surfaces,  without  causing  any  wart  formation, 
that  the  contagiousness  of  warts — to  whatever  agent  it  may  be  due — is 
easily  destroyed. 

It  accords  with  this,  that  the  contagious  properties  of  these  warts  are 
seldom  very  noticeable  ;  and,  as  is  well  known,  after  a  variable  time,  and 
under  circumstances  as  yet  not  clearly  defined,  they  commonly  disappear 
"  spontaneously."  Here  attention  may  be  called  to  the  not  very  rare 
occurrence  of  the  outbreak  of  warts  on  the.  hand,  after  the  making  of 
post-mortem  examinations  and  other  similar  work. 

1  British  Jour  mil  of  Dermatology,  1891,  vol.  iii.,  p.  186. 

2  J.  de  Clin.  ct  de  therap.  inf.,  Paris,  1894,  vol.  ii.,  p.  529 ;  also  vol.  i.,  1890,  p.  97. 

3  "  Surgical  Pathology,"  1879,  p.  668  (Hackley's  translation). 

4  Lkutsche  med.  Woch.,  May  18,  1899. 

5  Proceedings  of  the  Laryngological  Society  of  London,  1903,  vol.  x. 

6  New   York  Medical  Record,  September  7,  1878. 

12 


178  THE  NATURAL  HISTORY  OF  CANCER 

Another  group  of  papillomatous  tumours,  which  arise  from  the  ovary 
and  its  vicinity,  manifests  a  higher  degree  of  contagiousness  than  its 
cutaneous  analogue.  When  fragments  of  these  growths  are  shed  into 
the  peritoneal  sac,  they  readily  become  engrafted  thereon,  so  that  very 
formidable-looking,  diffuse  masses  of  these  warts  may  be  thus  produced. 
After  removal  of  the  original  disease,  and  detachment  of  the  more 
prominent  secondary  masses,  together  with  irrigation  and  drainage,  these 
growths  generally  completely  disappear.  Very  extensive  formations  of 
this  kind,  may  even  sometimes  disappear  spontaneously,  of  which 
Cullingworth  i  and  others  have  described  striking  examples. 

The  facility  with  which  accidentally  detached  grafts  from  these  tumours 
take  root  in  the  track  of  operation  wounds,  is  well  known  to  surgeons. 

In  a  case  of  this  kind,  with  considerable  abdominal  distension  from 
intraperitoneal  fluid  etc.,  for  which  Cullen2  was  obliged  to  resort  to 
paracentesis,  papillary  growths  soon  afterwards  developed  along  the 
whole  length  of  the  trocar  wound.  Similar  transplantation  warts  have 
often  been  known  to  form,  in  the  scar  of  the  operation  wound  in  the 
abdominal  wall ;  and,  in  fact,  anywhere  in  the  track  of  the  operation 
wound.  Most  recurrences  after  ablation  are  no  doubt  of  this  nature. 

From  these  clinical  experiences,  it  is  safe  to  predict  that  if  warts  of 
this  kind  were  finely  chopped  up,  and  the  product  injected  subcutaneously, 
the  disease  could  easily  be  artificially  transplanted  in  the  same  individual. 

There  is  yet  another  common  form  of  papilloma,  which  fairly  often 
manifests  contagious  properties,  and  is  transmissible  to  the  same  and  to 
other  persons  ;  and  this  is  the  venereal  condyloma.  This  malady  is  still 
commonly  regarded  as  a  gonorrhoeal,  chancrous,  or  syphilitic  manifesta- 
tion ;  but  this  is  I  believe  a  mistake. 

Condylomata  are  not  uncommonly  transmitted  with  gonorrhoea  and 
syphilis  ;  but  the  maladjr  is  sui  generis,  and  occurs  independently,  of  which 
there  are  unmistakable  instances.  It  is  curious  to  find  that  this  was 
also  the  opinion  of  Astley  Cooper  ;  thus,  in  his  vivacious  and  interesting 
"  Lectures  on  Surgery,"  3  he  says  :  "  These  warts  were  formerly  considered 
as  syphilitic,  but  you  are  to  learn  that  they  are  nothing  but  a  local 
disease,  requiring  nothing  but  local  means  for  their  cure.  Yet,  when  I 
say  local,  I  must  observe  that  they  frequently  secrete  a  matter,  which  is 
able  to  produce  a  similar  disease  in  others.  I  have  known  two  instances 
of  this.  Mr.  Chandler  removed  some  warts,  which  were  of  a  very  large 
size,  from  a  patient  in  the  hospital ;  and,  as  he  was  returning  the  knife, 
his  dresser  put  his  hand  forwards,  and  it  entered  just  under  the  thumb- 
nail. In  a  little  time  he  had  an  irritation  about  the  nail,  and  a  wart  grew 
out  of  the  part  where  the  puncture  had  been  made.  It  was  frequently 
destroyed  ;  but  each  time  it  grew  again.  I  advised  him  to  put  on  a 
blister,  for  the  purpose  of  bringing  away  the  nail,  and  then  that  the  wart 
might  be  removed.  He  applied  a  blister,  and  readily  removed  the  nail ; 
but  it  also  brought  away  the  wart,  which  never  grew  again." 

"  The  other  case  of  warts  generating  themselves,  was  told  me  by  a 
gentleman  in  Sussex.  He  was  called  to  attend  a  lady  in  labour  ;  he 

1  Transactions  of  the  Obstetrical  Society,  London,  vol.  xxxiv.,  p.  lot. 

2  "  Cancer  of  the  Uterus,"  1901,  p.  662.  3  P.  556. 


THE  EXPERIMENTAL  STUDY  OF  CANCER  GENESIS     179 

felt  something  in  the  vagina,  which  appeared  unintelligible,  and  on 
examination  found  it  to  be  a  crop  of  warts.  He  delivered  her,  but  did 
not  say  anything  about  the  warts  to  the  lady.  In  conversation  with  the 
husband,  he  told  him  that  his  lady  had  a  number  of  warts.  The 
gentleman  stated,  that  at  the  time  he  was  married  he  had  warts  on  the 
penis  ;  and  he  had  no  doubt  that  he  had  communicated  them  to  his  wife. 
It  is  a  common  opinion  that  they  are  propagated  by  the  blood,  but  do 
not  entertain  this  idea — it  is  by  the  secretion  of  matter." 

The  nature  of  the  contagium  in  these  cases  is  still  a  moot  question  ; 
but,  as  previously  mentioned,  there  are  reasons  for  believing — whatever 
it  is — that  it  centres  in  the  epidermoidal  cells  themselves. 

It  should  also  be  noted  that  these  warts — like  their  ovarian  congeners 
— often  recur  after  removal  by  surgical  means.  Their  structure  comprises, 
besides  the  papillomatous  outgrowths,  epidermoidal  ingrowths  and 
"  nests."  Yet  it  not  unfrequently  happens,  after  a  time,  that  they 
undergo  spontaneous  resolution. 

In  this  connexion,  it  is  interesting  to  recall  the  fact,  that  similar 
contagious  growths  affect  the  genitalia  of  dogs  and  other  animals  ;  and 
are  readily  transferred  from  one  animal  to  another  during  sexual  inter- 
course, and  by  experimental  implantation. 

Like  their  human  congeners,  these  growths  after  a  time  commonly 
disappear  spontaneously  ;  and  such  individuals  are  then  immune  to 
reinfection  (Sticker).  It  is  generally  believed  that  they  cannot  be  trans- 
planted into  any  other  animals  except  dogs  ;  but,  according  to  Sticker, 
a  case  is  known  in  which  a  fox  was  successfully  affected  in  this  way. 

The  history  of  the  building  up  of  our  knowledge  with  regard  to  this 
canine  malady  is  very  instructive,  especially  in  that  the  morbid  appear- 
ances on  histological  examination  have  been  so  diversely  interpreted  ; 
thus,  the  malady  has  been  described  by  those  who  have  specially  studied 
it  as  epithelioma,  carcinoma,  sarcoma,  lympho-sarcoma,  lymphoma, 
endothelioma,  papilloma,  granuloma,  molluscoid  etc. 

According  to  Sanfelice l  the  malady  is  a  blastomycosis ;  while 
J.  J.  Clarke  2  claims  it  as  a  sporozoan  infection. 

This  shows  how  little  the  histological  analysis  per  se,  can  be  depended 
on  for  diagnosis,  in  doubtful  cases  ;  and  it  should  make  us  very  cautious 
about  accepting  as  true  cancer,  the  somewhat  similar  lesions  met  with  in 
mice  and  rats. 

It  was  Wehr3  who  first  specially  called  attention  to  these 
tumours,  by  announcing  that  he  had  succeeded  in  experimentally 
producing  "  cancer,"  by  implantation  of  the  disease  from  the  vagina  and 
penis  into  the  subcutaneous  tissue  of  the  abdomen  of  other  dogs.  Of 
twenty-six  experiments,  twenty-four  succeeded  ;  but,  in  most  cases, 
these  grafts  subsequently  underwent  spontaneous  resolution.  In  one 
case,  however,  the  disease  progressed,  with  the  formation  of  secondary 
growths  in  the  adjacent  lymph-glands  and  in  the  spleen. 

Duplay  and  Cazin,4  who  studied  the  malady  in  1894,  successfully 

1  Eif.  Med.,  1904.  2*  "Protozoa  and  Disease,"  part  ii.,  1908. 

3  Arch.  f.  klin.  Chir.,  1889,  Bd.  xxxix.,  S.  226. 

4  Transactions    of    the    Eleventh    International    Medical    Congress,   Rome,    1894, 
vol.  ii.,  p.  103. 

12—2 


180  THE  NATURAL  HISTORY  OF  CANCER 

transplanted  bits  of  a  growth  from  a  dog's  penis,  into  the  subcutaneous 
tissue  of  other  dogs.  They  describe  the  disease  as  infective  granuloma. 
They  also  met  with  dissemination  in  one  case  (testis). 

Geissler 1  subsequently  made  successful  implantations  ;  and,  after  one 
experiment,  secondary  growths  in  internal  organs  were  found.  Like 
Wehr,  he  regarded  the  malady  as  a  malignant  epithelial  tumour. 

Smith  and  Washbourn  2  made  a  very  thorough  study  of  the  condition 
a  few  years  later.  They  found  that  in  the  vagina  the  tumours  often 
attained  a  large  size,  infiltrated  the  walls  deeply,  and  were  frequently 
ulcerated.  In  some  cases  secondary  deposits  were  found  in  the  adjacent 
lymph-glands,  liver,  and  spleen.  They  made  many  succsseful  trans- 
plantation experiments,  but  some  animals  were  found  to  be  immune.  In 
several  instances  they  witnessed  spontaneous  resolution,  the  subsidence 
often  being  concomitant  with  ulceration.  Dogs  that  recovered  after 
inoculation,  were  found  to  be  immune  to  fresh  grafts.  These  authors 
considered  the  disease  to  be,  small  round-celled  sarcoma. 

White3  regarded  the  tumours  as  "warty  growths,"  very  different 
from  any  known  form  of  human  sarcoma ;  and  by  Sticker 4  the  condi- 
tion is  described  as  lympho-sarcoma. 

Seligmann  5  has  lately  reported  other  instances  of  this  malady,  which 
he  describes  as  "  infective  tumours  "  ;  in  one  of  these  cases,  the  disease 
disseminated  from  the  prepuce  to  the  testis. 

It  is  evident  from  the  foregoing  profession  of  faith,  that  pathologists 
still  lack  a  really  satisfactory  criterion  for  malignancy  in  general,  as  well 
as  for  particular  varieties  of  malignancy. 

It  is  probable  that  growths  of  somewhat  similar  nature  are  common 
enough,  under  certain  conditions,  in  other  kinds  of  animals,  especially  in 
rats  and  mice. 

Of  like  nature  with  the  foregoing,  are  the  contagious  papillomata  of 
the  mouth  of  dogs  ;  which,  as  shown  by  Penberthy  6  and  others,  spread 
among  dogs  kennelled  together.  This  malady  is  also  communicable  by 
experimental  implantation  ;  and,  after  a  time,  it  is  apt  to  undergo 
spontaneous  resolution,  such  animals  then  being  immune. 

The  malady  seems  to  have  some  similitude  with  the  "  sublingual 
tumour "  of  human  nurselings,  which  is  a  papillary  outgrowth,  as 
described  by  Riga  and  Fede. 

Not  many  implantation  experiments  have  been  reported  with  other 
kinds  of  non-malignant  tumours  ;  but  Loeb  7  essayed  the  transplantation 
of  a  solid  adenoma  from  the  mamma  of  a  rat,  into  other  parts  of  the  same 
animal  and  into  other  rats,  with  negative  results  ;  except  that  in  one 
case,  the  graft  into  a  pregnant  animal  increased  until  young  were  born, 
when  it  quickly  dwindled  away. 

Lanz's 8  grafting  experiments  with  various  benign  tumours,  all  gave 
1  "  Verhandl.  d.  deutsche  Gesellsch.  f.  Chir.,  1895"  (Twenty-fourth  Congress,  Berlin), 

Transactions  of  the  Pathological  Society,  London,  1897,  vol.  xlviii.,  p.  310. 

British  Medical  Journal,  1902,  vol.  ii.,  p.  176. 

Zeits.  f.  Krebsforschung,  1904,  Bd.  i.,  S.  418  ;  also  ibid.,  Bd.  iv.,  Heft  2. 

Transactions  of  the  Pathological  Society,  London,  December,  1906. 

Journal  of  Comparative  Anatomy,  1898,  vol.  xi.,  p.  363. 

Journal  of  Medical  Research,  1902,  vol.  viii.,  p.  74.  8  Op.  cit. 


THE  EXPERIMENTAL  STUDY  OF  CANCER  GENESIS     181 

only  negative  results.  Mayet,1  however,  claims  to  have  produced 
sarcoma  in  a  dog,  by  the  injection  of  a  filtered  solution  of  myoma  of  the 
uterus  of  a  woman. 

It  seems  to  me  that  the  time  has  now  come  for  clearly  recognizing 
the  fact,  that  there  are  many  noxious  agents,  extrinsic  as  well  as  intrinsic, 
capable  of  exciting  the  tissue  cells  to  proliferative  activity.  In  the  face  of 
such  evidence  as  I  have  already  adduced,  and  of  such  additional  evidence 
as  I  have  still  to  supply,  the  dictum  of  Weigert  —  supported  as  it  is  by 
Ziegler  and  other  pathologists  —  that  irritants  ab  extra  are  incapable  of 
causing  formative  reactions,  needs  modification.  Borrel's  researches,2 
supported  as  they  are  by  many  converging  indications,  specially  point  in 
this  direction  ;  thus  he  has  shown,  that  the  proliferative  activity  of  the 
epithelial  cells  of  cancerous  tumours  has  many  analogies  in  other  morbid 
conditions,  such  as  occur  in  molluscum  contagiosum,  Darier's  disease, 
vaccinia,  sheep  small-pox  ("  la  clavelee  ")  etc.,  to  none  of  which  the 
least  suspicion  of  malignancy  attaches. 

In  molluscum,  which  is  an  epidermoidal  new  formation,  many  of  the 
morphological  appearances  of  cancer  are  met  with,  e.g.,  irregular  epithelial 
hyperplasia  with  budding  ingrowths,  excessive  keratinization  etc.  ;  and, 
microscopically,  various  mi  to  tic  irregularities,  cell  inclusions  etc.  The 
contagious  nature  of  the  malady  has  been  noted  by  many  observers  ; 
while  others  have  proved  its  transmissibility  by  experimental  means  : 
thus  Pick  inoculated  some  of  the  tumour  contents  into  a  boy  and  girl,  / 
and  ten  weeks  later,  characteristic  tumours  developed  at  the  seats  of 
inoculation,  and  subsequently  others  formed.  No  one,  however,  has 
succeeded  in  isolating  or  cultivating  any  causative  microbe.  Marx  and 
Sticker  claim  to  have  proved  that  the  infective  agent,  whatever  it  may 
be,  is  sufficiently  minute  to  pass  through  filters  which  retain  ordinary 
microbes. 

It  was  formerly  overlooked,  that  various  noxious  agents  may  cause 
the  formation  of  quasi-malignant  tumours  in  mankind  and  in  animals, 
e.g.,  quasi-epitheliomatous  lesions  due  to  blastomycosis,  as  in  cases  re- 
ported by  Gilchirst,  Owens,  Hyde  Hektoen  etc.  ;  and,  in  animals,  such 
tumour-like  new  formations  as  are  seen  in  coccidial  disease  of  the  rabbit's 
li  ver  ;  and  sarcoma-like  tumours,  due  to  actinomycosis  and  blastomycosis, 
such  as  Busse,  Curtis,  and  others  have  recorded.  The  recollection  of  these 
conditions,  will  serve  as  a  good  introduction  to  the  experimental  study 
of  malignant  tumours,  especially  when  we  add  thereto  the  remarkable 
instance  of  the  infective  papillomata  of  dogs,  so  often  mistaken  for  cancer. 


Experiments  with  Malignant  Tumours.  |>  \- 

During  the  last  twenty  years,  an  immense  number  of  workers  in  th's 
field,  claim  to  have  artificially  produced  malignant  tumours  :  (1)  by 
inoculation  of  cultures  of  various  so-called  "  cancer  microbes  "  ;  and 
(2)  by  diverse  kinds  of  tumour-tissue  grafting  etc. 

1  C.  R.  de  I'Acad.  des  Sci.,  1905. 

2  "  Epithelioses  infectieuses  et  epitheliomas,"   Ann.  de  I'Inst.  Pasteur,  1903,  xvii., 
p.  81. 


182  THE  NATURAL  HISTORY  OF  CANCER 

With  regard  to  most  of  these  claims,  supported  as  they  are  by  detailed 
accounts  of  the  histological  analysis  of  the  tumours,  they  only  show  how 
utterly  unreliable  such  findings  are,  as  evidence  of  the  real  nature  of  the 
malady  in  doubtful  cases. 

In  dealing  with  these  claims,  the  need  for  caution  is  very  manifest ; 
for,  in  this  branch  of  pathological  work,  more  perhaps  than  in  any  other, 
experience  is  apt  to  be  deceptive  and  judgment  difficult. 

As  to  the  first  group  of  experiments,  their  history  will  be  recorded 
in  the  sequel  ; l  hence,  all  that  need  be  noted  here  is,  that  their  futility 
is  now  generally  recognized,  most  of  them  having  already  passed  out  of 
recollection. 

It  is  with  the  second  group  of  claims  that  we  now  have  to  deal ;  and, 
at  the  outset,  I  may  as  well  state  my  conviction,  that  none  of  them  have 
scientific  validity. 

Most  of  those  who  have  been  engaged  in  this  kind  of  work,  have  been 
so  absorbed  in  their  own  undertakings  and  prepossessions,  that  they 
have  seldom  been  able  to  gauge  aright  the  scientific  value  of  their  own 
findings,  as  is  abundantly  testified  by  such  review  of  their  work  as  I  have 
previously  mentioned  ;  and,  as  is  still  more  emphatically  confirmed,  by 
the  further  examples  I  will  now  proceed  to  adduce. 

The  evidence  bearing  on  this  subject  may,  for  convenience  of  dis- 
cussion, be  grouped  under  the^  following  heads  : — 

(a)  Grafting  of  human  cancer  into  animals  ; 

(b)  Grafting  cancer  as  between  animals  of  the  same,  and 

(c)  Of  different  species  ; 

(d)  Transmissibility  of  cancer  from  one  human  being  to  another  ;  and 

(e)  Auto-implantation. 

(a)  Grafting  Human  Malignant  Tumours  into  Animals  etc. 

Of  the  numerous  attempts  that  have  been  made  from  time  to  time, 
to  transmit  human  malignant  tumours  experimentally  to  animals — 
whether  by  grafting,  inoculating  with  the  juice,  magma  etc.,  by  intra- 
venous injection,  and  other  ingenious  methods — the  results  have  almost 
invariably  been  negative. 

Among  the  earlier  experimenters,  only  Langenbeck,2  Follin,3  C.  0. 
Weber,4  and  Goujon,5  claim  each  a  single  successful  result. 

Langenbeck  injected  the  creamy  juice  of  a  recently  removed  malignant 
tumour  of  the  human  humerus,  mixed  with  defibrinated  blood,  into  the 
femoral  vein  of  a  dog.  The  injection  induced  intense  dyspnoea,  which 
soon  subsided  ;  so  that  a  week  later,  the  animal  seemed  in  fairly  good 
health.  Subsequently  emaciation  set  in,  and  the  animal  was  killed  in 
this  state,  sixty-three  days  after  the  injection.  The  post-mortem 
examination  revealed  several  small,  hard  nodules,  varying  in  size  from 

Q.v.  Chapter  X. 

"Schmidt's  Yahrbiicher  d.  gesam.  Med.,"  1840,  Bd.  xxv.,  S.  104. 
Lebert's  "  Traite  pratique  des  maladies  cancereuses,"  1851,  p.  136. 
"  Chirurgische  Erfahrungen  und  Untersuchungen,"  Berlin,  1859,  S.  289. 
These  de   Paris,    1866  :  "  Expose  de   quelques   faits  tendant  a  demontrer  que  les 
cancers  de  l'homme,"  etc. 


THE  EXPERIMENTAL  STUDY  OF  CANCER  GENESIS      183 

an  almond  to  a  lentil,  at  the  surface  of  each  lung ;  and  a  similar  small 
nodule  in  the  middle  of  the  left  lung.  Histologically  examined,  these 
nodules  resembled  in  structure  the  tumour  of  the  humerus,  whence  the 
juice  used  for  injection  was  derived. 

Follin  repeated  Langenbeck's  experiment  by  injecting  into  the 
jugular  vein  of  a  dog,  a  magma  derived  from  a  recurrent  cancerous  mass, 
recently  removed  from  the  axilla  of  a  woman,  whose  breast  had  been 
previously  extirpated  for  cancer.  On  the  fourteenth  day  after  the 
injection,  the  dog  was  killed  ;  and,  on  examining  the  body,  several  small 
firm  nodules  were  found  in  the  lungs,  in  the  walls  of  the  heart,  and  in 
the  liver.  These  formations  were  seldom  larger  than  a  pin's  head  ;  and, 
histologically,  they  were  found  to  comprise  "  cancer  cells." 

The  nodules  in  these  cases,  were  probably  nothing  but  consolidating 
inflammatory  lesions,  around  embolic  tumour  grafts  artificially  produced 
by  the  intravenous  injections.  Had  more  time  been  allowed,  they  would 
probably  have  completely  disappeared.  Such  was  actually  the  course  of 
events,  in  the  many  similar  experiments,  subsequently  made  by  Virchow, 
Vogel,  Wyss,  Billroth,  and  others.  In  these  cases,  the  animals  experimented 
on  were  not  killed  until  several  months  after  the  injection  ;  when  no 
trace  of  cancer  nodules  could  be  found  in  any  part  of  their  anatomy. 

The  positive  results  of  the  other  experimenters,  are  even  less  con- 
vincing than  the  foregoing. 

Dupuytren a  fed  dogs  and  other  animals  for  considerable  periods  with 
human  malignant  tumours,  but  they  did  not  acquire  the  disease  ;  and 
the  dogs  that  Alibert  caused  to  swallow  discharge  from  cancerous  ulcers 
etc.,  experienced  similar  immunity.  Shattock  and  Ballance2  have,  in 
like  manner,  fed  white  rats  for  several  months,  with  fresh  cancers  of  the 
female  breast,  with  only  negative  results. 

In  comparatively  recent  times,  several  additional  examples  of  this 
kind  of  experiment  have  been  reported  ;  but,  almost  invariably,  the 
results  have  been  negative  ;  thus  of  the  numerous  attempts  made  by 
Sticker3  and  Hemmeter,4  to  implant  human  cancer  into  dogs,  cats,  guinea- 
pigs  etc.,  all  were  unsuccessful. 

In  judging  the  value  of  the  alleged  positive  results,  it  is  necessary  to 
bear  in  mind  that  quasi-malignant  tumours  of  parasitic  origin — to  which, 
as  we  now  know,  humanity  is  liable — may  have  been  used,  some  of  which 
are  known  to  be  inoculable  :  for  instance,  the  quasi-sarcomatous  tumour  of 
the  thigh,  described  by  Curtis  5 — which  was  due  to  blastomycetic  infection 
— was  easily  inoculated  into  various  animals  ;  and  it  is  the  same  with 
the  still  commoner  quasi-malignant  tumours  due  to  actinomycosis  (as 
shown  by  the  experiments  of  Wolff  and  Israel),  tuberculosis,  and  other 
infective  parasitic  pseudo-plasms. 

Subjoined  are  some  examples,  of  the  more  notable  of  these  alleged 
positive  transplantation  experiments. 

Into  the  peritoneal  cavity  of  a  white  rat,  Dagonet6  injected  a  m&lange 

1   Oaz.  Med.  de  Paris,  1838,  p.  47.  2  British  Medical  Journal,  1891,  vol.  i.,  p.  567. 

3  Zeits.  f.  Krebsforschung.,  1904,  S.  413. 

4  American  Journal  of  Medical  Science,  April,  1903. 
6  Ann.  de  I'Inst.  Pasteur,  1896,  t.  x.,  p.  449. 

6  Arch,  de  Med.  Exp.,  etc.,  May,  1904. 


184  THE  NATURAL  HISTORY  OF  CANCER 

of  a  cancerous  lymph-gland,  secondary  to  epidermoidal  cancer  of  the 
penis,  in  saline  solution.  After  some  months,  the  animal  began  to  emaciate 
progressively  ;  and  died  thus,  fifteen  months  after  inoculation.  Multiple- 
nodules  were  then  found  in  the  omentum,  spleen,  and  liver,  which  were 
of  similar  structure  to  the  original  human  tumour.  Considering  the 
great  procli vity  of  white  rats,  kept  in  captivity,  to  develop  quasi-malignant 
tumours  spontaneously,  or  by  contagion  from  other  rats,  of  which  more 
anon,  it  seems  likely  that  this  is  the  explanation  of  the  tumours  found  in 
this  case,  especially  as  the  peritoneum  was  free  from  the  disease. 
The  very  numerous  experiments  of  this  kind,  that  have  been  made 
by  other  observers,  with  only  negative  results,  also  point  to  this  con- 
clusion. 

By  injecting  the  ascitic  fluid  derived  from  a  patient  with  colloid 
cancer  of  the  peritoneum,  into  the  jugular  vein  of  a  guinea-pig,  Gaylord  x 
found — when  the  animal  was  killed  three  and  a  half  weeks  after  the 
jnjection — a  small  nodule  in  one  lung,  which  he  considered  to  be  "  adeno- 
carcinoma."  Subsequently  numerous  other  experiments  of  this  kind 
were  made,  with  a  similar  result  in  a  few  cases.  In  a  dog  thus  treated, 
he  found — when  the  animal  was  killed  ninety  days  after  the  injection — 
numerous  "  cancerous  "  nodules  in  the  liver.  Subsequently  Hansemann 
histologically  examined  the  pulmonary  nodule,  but  could  find  no  evidence 
of  its  cancerous  nature.  In  one  of  the  above  cases,  the  ascitic  fluid  was 
kept  for  two  weeks  in  an  incubator,  before  it  was  used  for  injecting  into  the 
jugular  vein  of  a  guinea-pig  ;  when  this  animal  was  killed,  fifty  days  later, 
nodules  of  "  beginning  cancer  "  were  found  in  its  lungs. 

Having  collected  the  ascitic  fluid  from  a  patient  with  colloid  cancer 
of  the  peritoneum,  and  kept  it  for  ten  days  in  an  incubator,  Pease2 
practised  intravenous  injection  of  this  fluid  into  guinea-pigs  ;  and,  in  one 
case,  when  the  animal  was  killed  three  and  a  half  weeks  later,  he  found  a 
nodule  of  "  adeno-carcinoma  "  in  the  lung. 

Lewin  3  claims  to  have  transmitted  human  ovarian  cancer  to  dogs  : 
while  Dagonet  and  Mauclaire4  also  claim  to  have  transplanted  human 
rectal  cancer  into  rats. 

Many  unsuccessful  attempts  have  been  made  to  produce  leukaemia 
experimentally ;  but  Lowitt 5  now  claims  to  have  succeeded,  by  intra- 
venous injection  of  material  from  leuksemic  organs  into  rabbits. 

By  implanting  into  rabbits,  guinea-pigs,  and  dogs,  various  human 
cancer  tissues,  Bosc  and  Vedel6  claim  to  have  produced  "cancerous" 
nodules  at  the  seats  of  inoculation. 

Herzog  7  has  many  times  tried  to  produce  malignant  epithelial  and  con- 
nective-tissue tumours,  in  rabbits  and  guinea-pigs,  by  injecting  triturated 
human  material  subqutaneously,  intra-peritoneally,  and  into  the  anterior 
chamber  of  the  eye,  but  without  success  ;  for,  although  in  some  cases 
nodules  formed  at  first,  they  subsequently  completely  disappeared. 

1   American  Journal  of  Medical  Science,  1901,  vol.  cxxi.,  p.  503. 
"  Public  Health  Papers  and  Reports,"  vol.  xxv.,  1900. 

3  Zeits.  f.  Krebsforschung.,    1906,  Bd.  iv.,  S.  55. 

4  Arch,  de  Med.  Exp.,  1904,  t.  xvi.,  p.  552. 

5  "Twentieth  Century  Practice  of  Medicine,"  1903,  vol.  xxi.  (suppl.).  p.  571. 

6  La  Semaine  Med.,  1898,  p.  166. 

7  Journal  of  Medical  Research,  1902,  vol.  viii.,  p.  74. 


THE  EXPERIMENTAL  STUDY  OF  CANCER  GENESIS     185 

Juergens  l  injected  into  the  peritoneal  cavity  of  rabbits,  a  magma 
derived  from  a  metastatic  sarcoma  of  the  human  cerebral  meninges. 
Three  months  later,  one  of  the  animals  was  found  to  have  a  tumour  in 
its  right  eye.  On  post-mortem  examination  a  month  later,  a  sarcomatous 
tumour,  the  size  of  a  hazel  nut,  was  found  there.  The  tumour  teemed  with 
coccidia-like  organisms.  This  is  probably  a  case  of  microbic  infection. 

In  another  rabbit,  in  which  bits  of  a  myxo-sarcoma  of  the  human 
ovary,  had  been  implanted  in  the  peritoneal  cavity,  tumours  were  found — 
when  it  was  killed  some  months  later — in  the  lungs,  small  and  large 
intestines.  These  tumours  also  teemed  with  coccidia-like  bodies. 

Juergens  also  claims  to  have  successfully  implanted  into  animals  frag- 
ments of  sarcoma,  taken  from  a  human  subject  three  days  after  death. 

Some  interesting  implantation  experiments  have  been  made  with 
human  melanotic  tumours. 

These  were  started  many  years  ago  by  Goujon,2  who  injected  sub- 
stances of  this  kind  into  various  animals.  At  the  seat  of  inoculation,  he 
noted  that  one  or  more  small  black  tumours  sometimes  formed.  Soon 
afterwards  pigment  appeared  in  the  adjacent  glands  ;  and,  at  a  subse- 
quent period,  in  more  remote  glands.  He  specially  notes  the  great 
augmentation  of  the  total  amount  of  pigment  which  ensued  after  the 
injection,  as  if  by  multiplication  of  living  pigment-producing  elements. 

By  injecting  triturated  human  melanotic  tumour  in  saline  solution,  s* 
into  the  spleen  of  a  guinea-pig,  0.  Lanz  3  found,  seven  weeks  later,  a  small 
pigmented  nodule  in  the  animal's  left  external  ear  ;  moreover,  all  the  -^ 
internal  organs  contained  a  large  amount  of  free  and  intra-cellular  pig- 
•ment,  i.e.,  there  was  diffuse  melanosis. 

Bosc  and  Vedel4  inoculated  guinea-pigs  with  human  melanotic  sarcoma  &- 
material,  subcutaneously  and  intra-peritoneally  ;  and  so  produced  in  >• ' 
them  nodules  of  melanotic  sarcoma. 

By  implanting  a  small  fragment  of  a  secondary  melanotic  sarcoma 
from  a  woman,  at  the  root  of  the  tail  of  a  mouse,  Pfeiffer5  produced  a 
melanotic  tumour  at  the  seat  of  implantation.  He  transplanted  frag- 
ments of  this  tumour  into  twelve  other  mice,  in  one  of  which  a  similar 
growth  developed.  Even  before  Goujon's  time  Klencke  (1843)  claimed 
to  have  successfully  transplanted  human  melanoma  into  horses  and  dogs. 

Juergens 6  had  previously  made  many  experiments  of  this  kind ; 
thus,  having  implanted  under  the  conjunctiva  of  a  rabbit's  eye,  a  small 
bit  of  recently  extirpated  human  melanoma,  a  fortnight  later  a  melanotic 
tumour  had  developed  at  th§  seat  of  implantation. 

Juergens   also  implanted,   in  the  peritoneal  cavity  of  six  rabbits,   y 
fragments  of  melanoma  from  the  human  pancreas,  with  the  result  that 
within  a  few  weeks,  each  of  these  animals  developed  intra-abdominal 
pigmented  tumours,  with  similar  nodules  in  the  pericardium  and  heart 
as  well,  in  one  case. 

All  these  new  formations  teemed  with  pigmentiferous  coccidia-like 
bodies. 

1  Berlin  klin.  Woch.,  No.  15,  1895,  p.  331  ;  see  also  pp.  465  and  747. 

2  "  Inoculabilite  des  elements  pigmentaires  ou  melaniques,"  Gaz.det  Htipitaux,  1867, 
p.  339. 

3  Deutsche  med.   Woch.,  May  18,  1899.  *  Op.  cit. 

5   "  Die  Protozooa  als  Krankheitserriger,"  Jena,  1891,  p.  204.  6  Op.  cit. 


186  THE  NATURAL  HISTORY  OF  CANCER 

In  this  connexion  it  is  interesting  to  recall,  that  Lancereux  found  the 
blood  of  patients  affected  with  disseminated  melanotic  tumours,  very 
rich  in  pigment-bearing  elements. 

Here  also  reference  may  be  made  to  the  little-known  facts  about 
melano-mycosis,1  and  its  experimental  transmissibility .;  as  well  as  to  the 
recent  experiments  of  Charrin  and  Le  Play,2  who  by  subcutaneous  and 
intra-peritoneal  injection  into  various  animals,  of  pure  cultures  of  the 
fungus  (Stearophora  radicicola),  which  grows  on  the  root  of  the  vine, 
produced  black-coloured  tumours  like  melanomata.  Bard3  also  has 
shown  the  parasitic  nature  of  certain  melanotic  tumours. 

Fischel' s  attempts  to  implant  human  melano-sarcoma  into  rats  all 
failed  ;  and  a  similar  fate  befell  Roux  and  MetchnikofFs  implantations  of 
the  same  morbid  substance  into  the  chimpanzee.4 

With  material  obtained  by  harpooning  fragments  of  human  cancers 
and  mashing  them  up,  Dubois  5  inoculated  animals  subcutaneously.  As 
a  result,  tumour-like  swellings  formed  soon  afterwards,  in  several  cases. 

Boinet 6  inoculated  a  series  of  forty  rats  intra-peritoneally  with  fresh 
human  malignant  tumours  ;  and,  a  month  later,  one  of  these  animals 
became  paraplegic,  and  died  thus  a  few  days  afterwards.  It  was  then 
found  to  have  two  cancerous  tumours  adherent  to  the  spine,  abave  the 
central  tendinous  part  of  the  diaphragm,  the  adjacent  dorsal  vertebrae 
and  liver  being  invaded,  and  the  spinal  cord  compressed.  Histological 
examination  of  these  nodules  showed  that  they  comprised  proliferating 
epithelial  elements,  similar  to  those  of  the  human  tumour,  whence  the 
material  used  for  inoculation  was  originally  derived. 

The  other  results  of  this  series  of  experiments  were  negative  ;  as  also 
were  numerous  subcutaneous  implantations  in  various  animals. 

Mayet7  claims  to  have  successfully  transmitted  human  cancer  to 
white  rats,  under  circumstances  which  preclude  the  possibility  of  tissue 
or  cell  grafts  being  concerned  in  the  process.  Thus,  by  repeated  subcu- 
taneous injections  of  a  glycerine  extract  of  aseptically  macerated  human 
cancer,  filtered  through  porcelain  or  asbestos,  he  has  several  times  pro- 
duced in  these  animals,  after  an  interval  of  some  months,  "  des  lesions 
cancereuses  epitheliales."  It  is  of  interest  to  remark  that  with  dogs  and 
rabbits,  similar  experiments  yielded  only  negative  results. 

Firket 8  implanted  fragments  of  human  sarcoma  into  rats ;  and,  five 
weeks  later,  in  several  cases,  tumours  developed  at  the  seats  of  inoculation. 

By  injections  of  cancer  juice  from  human  malignant  tumours  into 
white  mice,  Francotte  and  De  Rechter9  claim  to  have  caused  the  formation 
of  cancerous  tumours,  some  months  later,  at  the  seats  of  inoculation. 

As  we  have  already  seen,  white  mice  and  rats  are  so  prone  to  originate 
quasi-cancerous  tumours  spontaneously,  that  the  causative  relation  of 
the  injections  to  the  tumours  in  these  cases,  is  by  no  means  evident. 

Among   those   who   have   essayed   to   transplant   human   cancer   to 

1  Transactions    of    the    Pathological    Society,    London,    vol.    xlii.,    1891,   p.   423 
(Delepine). 

2  G.  R.  de  I'Acad.  des  Sci.,  1905.  3  Lyon  Mid..  1885,  t.  xlviii.,  p.  407. 
*  Butt,  de  I'Acad.  de  Med.,  1903,  p.  3.         5  Bulletin  Med.,  August  16.  1896. 

6  La  Semaine  Med.,  June  13,  1894. 

7  Lyon  Med.,  1905,  p.  1356  ;  also  ibid.,  December  11,  1904,  and  August  19,  1893. 

8  La  Semaine  Med.,  1893,  p.  8.          9  Bull.  R.  Acad.  de  Med.  de  Belgique,  1892,  p.  999. 


THE  EXPERIMENTAL  STUDY  OF  CANCER  GENESIS     187 

various  animals,  with  negative  results,  mention  may  be  made  of  Duplay 
and  Cazin,  Shattock  and  Ballance,  Senn,  Weigert,  D'Arcy  Power,  Senger, 
Fischel,  Wickham,  Klebs,  D'Anna  etc. 

Shattock  and  Ballance  x  undertook  many  experiments  to  this  end, 
implanting  portions  of  quite  fresh  human  malignant  tumours  into 
monkeys,  dogs,  rats,  cats,  and  sheep  ;  but  the  results  were  always 
negative  ;  hence  they  concluded  that  it  is  impossible  to  transmit  the 
human  disease  to  animals. 

In  two  of  their  experiments,  entire  scirrhous  cancers  of  the  female 
breast  were  inserted  into  the  abdominal  cavity  of  animals,  and  disappeared 
after  a  time  without  leaving  a  trace  ;  in  like  manner,  large  slices  of  chondri- 
fying  round-celled  sarcoma  of  the  humerus — when  similarly  treated — 
completely  disappeared. 

Having  in  view  the  immense  preponderance  of  negative  results  and 
the  many  sources  of  fallacy,  to  some  of  which  I  have  previously  referred — 
I  can  only  regard  the  alleged  successes  in  this  kind  of  experiment,  as 
resting  on  insufficient  evidence  to  ensure  credibility. 


(b)  Grafting  Experiments  as  between  Animals  of  the  Same  Species. 

It  seems  reasonable  to  suppose  that  implantation  experiments  might 
have  a  better  chance  of  success,  if  confined  to  animals  of  the  same 
species ;  but,  in  this  direction  also,  most  experiments  have  proved 
abortive  (Bert,  Jeannel,  Gratia,  Senn,  Kb'ster,  Erbre,  Doultrelepont,  and 
many  others). 

In  comparatively  recent  times,  however,  several  experimenters  allege 
that  they  have  succeeded  in  transmitting  "  cancer  "  from  mouse  to  mouse, 
and  from  rat  to  rat.  What  is  the  real  nature  of  this  so-called  cancer  ? 

The  great  mistake  of  those  who  have  so  prematurely  identified 
"  Jensen's  mouse  tumour  "  with  cancer  is,  that  in  making  their  diagnosis 
they  have  placed  far  too  much  reliance  on  histological  appearances — the 
fallaciousness  of  which  has  so  often  been  demonstrated  in  recent  times — 
and  far  too  Little  on  the  ensemble  of  the  indications  available  for 
diagnostic  purposes. 

It  was  by  following  this  line  of  fallacies  that  Wehr,  Smith  and  Wash- 
bourn,  and  others,  formerly  persuaded  themselves  and  the  majority  of 
pathologists,  that  the  infective  venereal  tumours  of  dogs  were  examples 
of  contagious  inoculable  cancer  ;  indeed,  it  is  only  lately  that  this  wide-     1 
spread  fallacy  has  been  exploded. 

Experimental  pathologists  are  only  now  beginning  to  recognize, 
although  pathological  anatomists  have  long  been  aware  of  it,  that 
epithelial  proliferations — in  their  structural  details  very  like  cancer — are 
of  common  occurrence  in  many  non-cancerous  conditions. 

These  considerations  alone  should  have  sufficed  to  cause  the  present 
subject  to  be  approached  with  the  greatest  caution,  but  the  event  has  been 
iar  otherwise  ;  for,  the  modern  experimenter  being  a  law  to  himself,  is 
only  too  often  quite  impervious  to  the  plainest  lessons  of  history,  even  to  v 
those  that  may  be  learnt  from  his  own  speciality.  This  narrowness  of 
outlook,  is  the  cause  of  the  extraordinary  concatenation  of  blunders  with 
1  Proceedings  of  the  Royal  Society,  London,  1890,  vol.  xlviii. 


188  THE  NATURAL  HISTORY  OF  CANCER 

which  the  history  of  the  experimental  study  of  cancer  is  cumbered  ; 
indeed,  if  we  put  aside  the  Miinchausen  creations,  very  little  solid  fact 
remains  as  the  outcome  of  so  much  vapouring. 

,  " .  ^p.  Now,  what  are  the  plain  facts  in  respect  to  which  "  Jensen's  tumour  " 
differs  in  toto  from  cancer,  or  any  form  of  human  malignant  tumour  ? 
They  are  briefly  these  : — 

The  disease  is  highly  contagious  ;   and  the  observations  of  many 

competent    pathologists    (Gaylord,    Borrel,    Haaland    etc.),    who    have 

specially  studied  this  aspect  of  the  malady  show,  that  when  infected 

animals  are  introduced  into  cages  with  healthy  animals,  the  latter  take 

^  -Vthe  malady  as  if  by  local  contagion. 

There  can  be  no  doubt  that  mice  kept  in  captivity,  especially  those 
confined  for  experimental  use  in  scientific  laboratories,  which  are  often 
numerous  and  get  but  little  hygienic  attention,  are  singularly  prone  to 
epidemic  outbreaks  of  "  cancer,"  as  signalized  by  Gaylord  and  Clowes,1 
Haaland,2  Borrel,3  Loeb  4  etc. 

As  long  ago  as  1891,  Morau5  found  that  mice  fed  with  a  paste  composed 
of  chopped-up  tumour  and  bread-crumbs,  developed  the  disease  ;  and  some 
recent  observations  of  Borrel,  as  to  the  spread  of  the  infection  through 
contaminated  water,  are  of  similar  import. 

Because  his  experience  of  this  occurrence  has  been  negative,  so  far  as 
evidence  of  contagion  is  concerned,  Dr.  Bashford  6  seems  to  think  that  this 
negative  experience  justifies  him  in  denying  point-blank  the  very  positive 
results  of  the  above-mentioned  pathologists,  which  he  ascribes  to  fallacious 
-  observations,  erroneous  deductions,  and  lack  of  personal  experience.  In 
my  opinion  this  criticism  is  unjustifiable,  and  without  scientific  warrant. 
Ifc  is  not  the  first  mistake  of  this  kind  that  Bashford  has  made  ;  for,  having 
denied,  as  the  result  of  his  own  negative  experience,  the  positive  results  of 
Clowes,7  as  to  the  immunity  of  mice — whose  tumours  had  undergone 
spontaneous  cure — to  reinoculation,  he  has  recently  had  to  eat  his  own 
words  ;  and,  so  long  as  this  vicious  kind  of  criticism  is  indulged,  similar 
results  may  be  anticipated. 

That  various  parasites  to  which  mice  are  specially  prone,  such  as 
sporozoa,  are  capable  of  originating  contagious  quasi-malignant  growths, 
we  know  from  the  researches  of  Borrel  and  others.  Yet  these  "  infective 
epithelioses  "  are  just  as  different  from  cancer,  as  are  the  coccidial  tumours 
of  the  rabbit's  liver,  with  which  they  are  really  analogous. 

As  Twort 8  has.  lately  indicated,  many  cases  of  so-called  "  cancer  "  in 
mice,  are  commonly  associated  with  invasion  of  the  part  by  sarco-sporidia 
(Miescher's  cylinders)  ;  while  the  extraordinary  facility  with  which  this 
/  sporozoan  muscle  parasite  can  be  transmitted  from  mouse  to  mouse,  by 
feeding  with  contaminated  muscle,  has  been  well  demonstrated  by 
T.  Smith.9 

1  British  Medical  Journal,  1906,  vol.  ii.,  p.  1555;  also  Journal  of  the  American 
Medical  Association,  1907,  p.  15. 

Ann.  de  I'Inst.  Pasteur,  1905,  vol.  xix.,  No.  3,  p.  156. 

C.  R.  Soc.  de  Biologie  de  Paris,  1905,  p.  770. 

Univ.  Penn.  Med.  Butt.,  U.S.,  April,  1907. 

C.  R.  Soc.  de  Biologie  de  Paris,  1891,  t.  iii.,  pp.  289,  721,  and  801. 

Lancet,  1907,  vol.  i.,  p.  802. 

British  Medical  Journal  1906,  vol.  ii.,  p.  1548. 

Transactions  of  the  Pathological  Society,  London,  1907. 

Journal  of  Experimental  Medicine,  May,  1905,  p.  429. 


THE  EXPERIMENTAL  STUDY  OF  CANCER  GENESIS     189 

Some  recent  observations  by  Borrel  x  seem  to  show  that  certain  of 
these  "  Jensen  tumours  "  are  formed  round  vermiform  parasites,  which 
end  their  existence  thus,  after  having  lived  for  a  time  in  the  animal's 
blood  ;  and  the  experiments  of  Rouget  have  shown  that  mice  and  rats  are 
very  prone  to  trypanosome  infection. 

In  this  connexion,  it  is  also  of  interest  to  note,  that  Borrel,  Gaylord  and 
Calkins  have  often  found  the  blood  of  these  tumours  teeming  with 
parasitic  spirochaetae. 

In  the  present  state  of  this  inquiry,  it  would  be  premature  to  speculate 
as  to  the  precise  value  of  these  significant  finds  ;  but  they  seem  to  point 
to  distinct  causative  agents  for  these  pseudo -plasms. 

Since  this  was  written  Jacobs  and  Geets,  by  inoculating  mice  and  T-£' 
rats  with  cultures  of  Doyen's  Micrococcus   neoformans,  claim  to  have 
produced  thus  similar  local  and  general  cancerous  tumours.  • 

By  exposing  pieces  of  "  Jensen's  tumour  "  to  the  very  low  tempera- 
tures generated  by  liquid  air,  Moore  and  Walker 2  lately  found  that 
these  tumours  nevertheless  retained  their  power  of  inoculability.  It  is 
well  knowri  that  many  microbes  and  spores  retain  their  vitality  even 
after  exposure  to  such  low  temperatures,  which  kill  the  tissue  cells. 
From  this  it  may  be  inferred,  that  the  infective  agent  in  these  tumours- 
is  of  parasitic  origin. 

There  is  no  evidence  as  to  the  occurrence  of  contagion,  such  as  is  met 
with  in  these  mice  pseudo-plasms,  in  any  form  of  human  cancer — at  least, 
not  outside  the  Miinchausen  sphere ;  but,  in  the  contagious  venereal 
malady  of  dogs,  analogous  conditions  are  commonly  met  with.  ';  Jensen's 
tumour  "  is  readily  transmissible  by  implantation  to  other  mice,  the 
proportion  of  successful  experiments  often  being  as  high  as  50  per  cent.  • 
indeed,  Morau — using  only  closely  related  animals — succeeded  in  80  per 
cent,  of  his  experiments. 

No  such  property  is  ever  manifested  by  human  cancer ;  but,  with  the 
contagious  venereal  pseudo-plasm  of  dogs,  similar  conditions  obtain. 

A  considerable  proportion  of  white  mice  are  immune  to  the  contagion 
of  this  disease,  whether  in  its  spontaneous  or  experimentally  determined 
form  ;  and  sometimes  whole  families  manifest  this  peculiarity.  The  same 
phenomena  have  often  been  noted  in  the  contagious  malady  of  dogs. 

Moreover,  "  Jensen's  tumour  "  fairly  often  undergoes  spontaneous 
resolution  ;  and  the  cured  animals  are  then  immune  to  further  contagion, 
giving  only  negative  results  when  inoculated,  as  Gaylord  and  Clowes  have 
specially  pointed  out.  With  human  malignant  tumours,  no  such  spon- 
taneous curability  has  ever  been  scientifically  demonstrated  ;  but,  with  the 
venereal  pseudo-plasms  of  dogs,  this  phenomenon  is  of  common  occur- 
rence. 

"  Jensen's  tumour  "  is  circumscribed  and  easily  enucleable,  the  tissues 
of  the  host  forming  no  part  of  it ;  moreover,  the  latter  do  not  acquire 
cancerous  properties,  nor  do  they  become  interpenetrated  by  processes 
of  the  pseudo-plasm;  and,  besides  this,  "Jensen's  tumour"  generally 
causes  no  cachexia. 

1  C.  R.  Soc.  de  Biologic  de  Paris,  1905,  p.  770 ;  also  British  Medical  Journal,  1906,. 
vol.  ii.,  p.  392. 

2  Lancet,  1908,  vol.  i.,  p.  226. 


190  THE  NATURAL  HISTORY  OF  CANCER 

Finally,  according  to  Apolant  and  Ehrlich,1  "  Jensen's  tumour  "  in  the 
course  of  experimental  transmission  often  changes  its  anatomical  type — 
from  the  epithelial  to  the  sarcomatous  etc.  ;  and  Morau  found,  under 
similar  circumstances,  that  its  physiological  type  also  changed,  with 
corresponding  alteration  in  its  power  of  inoculability.  Lately  from 
"  adeno-carcinomata,"  inoculable  "  sarcomata,"  and  "  sarco-carcino- 
mata  "  of  mixed  type,  have  been  obtained ;  and  these  latter  have  again 
produced  "  pure  sarcomata  "  ;  while  these  malignant  formations  have 
been  found  to  revert  to  "  benign  adenoma." 

In  all  of  these  vitally  important  respects,  which,  taken  together,  are 
crucial  for  diagnostic  purposes,  "  Jensen's  tumour  " — whatever  its  real 
nature  may  eventually  turn  out  to  be — is  totally  unlike  any  form  of 
human  cancer. 

jQn  the  other  hand,  like  the  venereal  malady  of  dogs,  "  Jensen's 
tumour  "  can  usually  be  successfully  grafted  into  other  animals  of  similar 
species. 

Another  feature  in  regard  to  which  the  two  maladies  present  a  certain 
resemblance  is,  that  in  both 'secondary  disseminative  lesions  occasionally 
result ;  so  that,  in  this  respect,  "  Jensen's  tumour  "  resembles  certain 
artificially  produced  pseudo-plasms — such,  for  instance,  as  those  San- 
felice,  O.  Schmidt,  Curtis,  Busse,  and  others  produced,  by  inoculating 
animals  with  certain  pathogenic  yeasts.2 

It  was  Morau,3  in  1891,  who  first  specially  directed  attention  to  this 
so-called  cancer  ("  epitheliome  cylindrique  ")  in  mice  ;  and  subjected  the 
malady  to  experimental  tests. 

The  original  tumour  developed  spontaneously  in  the  subcutaneous 
tissue  of  the  axilla  of  a  captive  white  mouse.  It  was  easily  enucleable, 
non-adherent  to  contiguous  structures,  and  caused  no  disturbance  of 
the  animal's  general  health.  A  portion  of  this -tumour,  immediately  after 
its  aseptic  ablation,  was  by  trituration  reduced  to  a  magma,  which  was 
forthwith  injected  into  the  subcutaneous  tissue  of  a  series  of  other  white 
mice.  About  three  months  afterwards,  it  was  noticed  that  nearly  all 
the  injected  animals  presented  similar  tumours  at  the  seats  of  inoculation 
and  elsewhere,  which  subsequently  slowly  increased  in  size.  One  of 
these  tumours  was  then  enucleated,  and  from  it  fresh  magma  was 
prepared,  with  which  another  series  of  mice  was  injected  ;  and  these 
also,  after  a  similar  interval,  acquired  the  disease.  Experiments  of  this 
kind  were  successfully  continued  through  several  generations. 

It  is  noticeable  that  the  animals  used  for  these  experiments  were  all 
of  the  same  strain,  closely  inter-related,  and  had  all  lived  in  the  same 
cages.  This  no  doubt  explains  the  very  large  proportion — over  80  per 
cent. — of  successful  implantations  ;  for,  when  animals  of  foreign  strains 
were  used,  the  proportion  of  successful  inoculations  was  much  less.  In 
subsequent  experiments  of  this  kind,  Morau  found  that  when  the  malady 
had  been  artificially  transmitted  through  a  considerable  number  of 
generations,  the  inoculability  of  the  tumour  markedly  diminished. 

1  Berlin,  klin.  Woch.,  1905,  xlii.,  S.  871 ;   ibid.,  1906,  No.  2  ;  also  Arbeit,  aus  k.  Inst. 
f.  exp.  Therap.  z.  Frankfurt-a.-M.,  1906,  S.  65  and  77. 

2  For  details,  vide  Chapter  X. 

3  C.  R  Soc.  de  Biologic,  Paris,  1891.  t.  iii.,  pp.  289,  721,  and  801 ;  also  Arch,  de  Med. 
exp.,  etc.,  September,  1894,  t.  vi.,  p.  677. 


THE  EXPERIMENTAL  STUDY  OF  CANCER  GENESIS     191 

Morau    seldom    noticed    dissemination,    except    after    traumatisnT< 
affecting  the  edge  of  the  tumour. 

No  cultures  could  be  obtained  from  any  of  the  many  tumours 
examined,  nor  could  any  microbes  be  discriminated. 

Attempts  to  transplant  the  malady  into  other  animals  than  mice  failed. 

Jensen  l  did  little  more  than  repeat,  extend  and  popularize  Morau's 
experiments,  which  in  the  intervening  decennium  had  been  forgotten. 
From  a  small  subcutaneous  tumour  on  the  back  of  a  white  mouse,  whose 
histological  structure  resembled  that  of  tubular  cancer,  he  took  pieces 
and  brayed  them  in  a  mortar  with  physiological  salt  solution.  Small 
quantities  of  this  melange  were  injected  subcutaneously  into  a  series  of 
white  mice,  with  the  result  that  tumours,  like  the  original,  developed  at 
the  seat  of  inoculation  in  most  cases.  Even  by  the  fourteenth  day  after 
injection,  small  nodules  were  visible  ;  and,  in  the  course  of  some  months, 
quite  large  tumours  had  formed — sometimes  as  large  as,  or  even  larger 
than,  the  affected  mouse.  The  tumours  were  transmitted  in  this  way 
through  over  twenty  generations  of  mice,  about  half  of  those  inoculated 
producing  tumours.  Some  animals,  and  even  entire  families,  were 
immune  ;  and  those  in  whom  first  injections,  failed,  yielded  negative 
results  to  further  injections. 

From  white  mice  the  disease  was  only  occasionally  and  with  difficulty 
transmitted  to  the  grey  kind  ;  and  negative  results  followed  all  attempts 
to  produce  it  experimentally  in  white  rats,  guinea-pigs,  rabbits,  goats 
and  ducks. 

Jensen  regarded  his  experimentally  produced  tumours  as  implantation 
grafts,  derivatives  of  the  transplanted  tumour  cells  ;  and  he  could  neither 
detect  any  microbes  in  the  tumours,  nor  get  any  cultures  of  such. 
Metastatic  tumours  were  not  noticed. 

Borrel 2  performed  many  similar  experiments  with  like  results.  In 
tumours  of  some  duration,  he  found  metastases  very  common,  especially 
in  the  lungs.  These  he  determined  arose  from  graft-like  cellular  emboli, 
detached  from  the  primary  tumour,  which  reached  the  lungs  by  the 
bloodvessels.  He  demonstrated  many  tumour  grafts  of  their  kind, 
within  the  pulmonary  bloodvessels. 

Haaland  3  and  Bashford  4  have  also  made  many  confirmatory  experi- 
ments of  this  kind  ;  but  without  otherwise  adding  to  our  knowledge  of 
the  malady,  the  real  nature  of  which  has  yet  to  be  determined. 

In  a  communication  published  subsequently  to  the  one  above  cited, 
Borrel5  has  reported  some  interesting  particulars  as  to  these  tumours. 
In  the  centre  of  each  nodule  he  has  commonly  found  marked  indications 
of  active  phagocytic  processes,  characterized  by  the  presence  of  large 
mono-nucleated  cells,  greatly  hypertrophied,  vacuolated,  and  "  bourrdesde 
detritus  de  toute  sorte."  In  the  vicinity  thus  characterized,  numerous  large 
blood  sinuses  abounded.  Around  the  central  area  the  epithelial  tubules, 
which  constituted  the  real  tumour,  were  disposed  in  a  radiating  manner. 
These  phagocytic  areas,  he  considers  due  to  small  vermiform  parasites, 

1  Hospitalstidente,  No.  19,  1902;  also  Nos.  21  and  22.  1903:  and  Zznt.  f.  Bakt.,  1903, 
Bd.  xxxiv.,  No3.  1  and  2. 

2  Ann.  de  I'Inst.  Pasteur,  1903,  vol.  xvii.,  p.  81.  3  Ibid.,  1905,  vol.  xix.,  p.  156. 

4  Scientic  Reports  of  Cancer  Research  Fund,  1904  and  1905. 

5  C.  E.  Soc.  de  Biologie  de  Paris,  1905,  t.  i.,  p.  770. 


192  THE  NATURAL  HISTORY  OF  CANCER 

which  end  their  existence  here  after  having  lived  for  a  time  in  the  animal's 
blood  ;  and  in  this  connexion  it  is  interesting  to  note,  that  he  has  often 
found  spirochaetae  in  the  blood  sinuses  of  these  tumours,  sometimes  in 
immense  numbers,  as  also  has  Ehrlich. 

Loeb,1  like  Apolant  and  Ehrlich,  also  claims  to  have  artificially  pro- 
duced carcinomatous  and  sarcomatous  tumours  in  Japanese  mice,  by 
inoculating  them  with  carcinomatous  growth,  derived  from  the  sub- 
maxillary  gland  of  a  Japanese  mouse. 

Like  mice,  rats  are  also  subject  to  a  quasi-malignant  kind  of  tumour, 
which  is  contagious,  transmissible  by  implantation,  and  in  other  respects 
much  resembles  the  above-described  malady  of  mice. 

Hanau  2  was  the  first  to  describe  and  experiment  with  this  pseudo- 
plasm.  He  injected  material  from  an  "  epidermoidal  cancer  "  of  the 
vulva  of  a  rat,  into  the  tunica  vaginalis  testis  of  two  other  rats  :  one  of 
these  died  seven  weeks  later,  with  diffuse  nodular  "  cancer  "  of  the 
peritoneum  ;  the  other  was  killed  eight  weeks  after  inoculation,  when  two 
"  cancerous  "  nodules  were  found,  one  in  the  adrenal,  the  other  in  the 
gubernaculum  testis.  With  material  from  one  of  these  nodules,  a  third 
rat  was  injected  ;  and  when  it  was  killed,  three  months  afterwards,  it 
presented  a  tumour  at  the  seat  of  injection,  as  well  as  diffuse  nodular 
growths  throughout  the  peritoneum,  and  in  the  posterior  mediastinum. 
All  of  these  tumours  were  histologically  of  similar  structure  to  the  original 
vulvar  tumour.  Hanau  considered  that  these  results  show,  "  successful 
grafting  of  tumour  tissue." 

Eiselsberg3  grafted  portions  of  a  "  fibro-spindle-celled  sarcoma  "  from 
the  back  of  one  rat,  into  the  peritoneal  cavity  of  two  other  rats  :  in  one  of 
these  a  large  pseudo-sarcomatous  tumour  of  the  peritoneum  developed, 
of  which  the  animal  died,  five  months  after  the  implantation.  In  its 
histological  structure,  this  latter  tumour  resembled  the  original. 

Velich  4  transplanted  portions  of  a  "  periosteal  sarcoma  "  of  the  femur 
of  a  white  rat,  into  series  of  other  rats,  through  nine  generations  ;  and,  at 
the  seat  of  implantation,  a  tumour  generally  formed,  which  structurally 
resembled  the  original  tumour.  In  one  instance  he  succeeded  in  thus 
transplanting  a  tumour  fragment,  twenty-four  hours  after  its  removal. 
After  several  generations  of  successful  transplantations,  the  power  of  the 
grafts  to  grow  underwent  great  diminution,  or  was  altogether  lost. 
Uninoculated  rats  kept  in  the  same  cage  with  their  inoculated  congeners, 
developed  similar  tumours.  Disseminative  tumours  were  not  seen  in  any 
of  these  inoculated  animals.  Injections  with  tumour  juice,  from  which 
the  cells  had  been  removed  by  filtration,  gave  only  negative  results. 

Loeb,5  with  material  derived  from  an  "  adeno-cystic  sarcoma  "  from 
the  thyroid  region  of  a  white  rat,  made  a  series  of  transplantations  into 
other  white  rats — chiefly  into  the  subcutaneous  tissue,  and  into  the 
peritoneal  cavity  ;  and,  in  most  cases,  at  the  seat  of  implantation,  a  tumour 
similar  in  structure  to  the  original  resulted.  Local  disseminative 

1  Penn.  Univ.  Med.  Bulletin,  July,  1906,  p.  113 

2  Corresp.  Bl.  f.  schw.  Aerzte,  1889,  No.  11,  S.  334. 

3  Wien.  klin.  Woch.,  1890,  Xo.  43,  S.  927. 
*    Wien.  med.  Blatter,  1898,  Nos.  45  and  46. 

8  Journal  of  Medical  Research,  1902,  vol.  viii.,  p.  46  ;  also  ibid.,  vol.  vi.,  p.  28. 


THE  EXPERIMENTAL  STUDY  OF  CANCER  GENESIS     193 

nodules  were  often  seen,  as  well  as  contact  implantation,  and  even  distant 
dissemination.  In  one  case,  after  excision,  the  disease  recurred  locally, 
with  dissemination  in  distant  parts.  In  a  few  cases  he  succeeded  in 
producing  similar  pseudo-plasms,  by  injecting  the  fluid  contents  of  the 
tumour  cysts,  which  contained  cellular  elements  ;  but,  after  these  had  been 
removed  by  filtration,  the  injections  were  always  negative.  In  a  fair 
number  of  cases  the  rats  used  proved  to  be  quite  immune.  Several 
experiments  were  made  to  determine  how  long,  after  removal,  the  grafts 
would  maintain  their  inoculability  ;  and,  by  keeping  them  on  ice,  they 
were  found  to  be  effective  even  after  five  days'  exposure. 

Attempts  to  implant  the  disease  into  white  mice,  guinea-pigs,  rabbits, 
and  other  animals,  all  failed  ;  but,  in  two  cases,  he  succeeded  in  trans- 
mitting it  into  a  hybrid  of  a  white  and  grey  rat. 

In  no  case  could  any  microbes  be  detected  in  the  tumours  ;  hence, 
Loeb  concluded,  that  the  latter  were  derived  from  the  transplanted  cells. 

Herzog  x  got  similar  results  in  a  series  of  over  fifty  implantations, 
comprising  eight  generations.  Fluid  extracted  from  these  tumours,  and 
made  ceU-  and  microbe-free  by  special  filtration,  when  injected  never  gave 
a  positive  result.  Attempts  to  implant  the  malady  into  rabbits  all  failed. 

Flexner  and  Jobling  2  have  also  successfully  implanted  mixed-celled 
sarcoma  of  the  vesicula  seminalis  of  a  white  rat,  into  other  white  and 
grey  rats,  with  the  formation  of  metastases  in  several  cases. 

Loeb  queries  :  "  Are  these  growths  sarcomata  or  granulomata  ?"  and 
he  decides  for  the  former  ;  but  to  me  it  seems,  for  reasons  previously 
mentioned,  that  the  ensemble  of  this  malady,  like  the  similar  affection 
of  mice,  is  totally  unlike  any  known  form  of  human  malignant  tumour. 

A  few  other  examples  of  the  alleged  successful  outcome  of  this  kind  of 
implantation  still  remain  to  be  mentioned. 

Thus,  in  the  course  of  attempts  to  transmit  cancer  from  dog  to  dog, 
Mathis,3  after  many  failures,  claims  a  single  success. 

In  this  case,  having  injected  material  from  "  thyroid  cancer  "  of  the 
dog,  into  the  same  part  of  another  healthy  dog,  a  tumour  developed  at  the 
seat  of  injection ;  which,  in  the  course  of  three  months,  attained  the  size 
of  a  pigeon's  egg.  Histologically  this  tumour  resembled  the  original  one. 

In  like  manner^  Arloing  and  Tripier4  succeeded  in  transplanting  a 
graft  of  mammary  "cancer"  from  one  dog  to  another;  and  Novinsky5 
grafted  bits  of  an  epithelial  alveolar  tumour  from  the  nose  of  one  dog, 
into  the  subcutaneous  tissue  of  another  dog — the  grafts  growing  into 
tumours  like  the  original,  in  two  out  of  forty-two  implantations.  Lately 
Bashford6  has  reported  similar  results. 

Goujon,7  having  grafted  epithelial  cancer  from  one  guinea-pig  into 
another,  maintains  that  the  latter  presented  at  the  seat  of  implantation 
an  almond-sized  tumour,  together  with  cancerous  nodules  in  the  viscera, 
when  it  was  killed  fifteen  days  after  the  operation. 

Journal  of  Medical  Research,  1902,  vol.  viii.,  p.  74. 

Cent.  f.  allgem.  Path.  u.  path.  Anal..  April  15.  1907. 

Rev.  des  Maladies  Cancereuses,  October,  1896,  p.  16. 

Lyon  Med.,  May  26,  1895,  p.  119. 

Cent.  f.  med.  Wiss.,  1876. 

British  Medical  Journal,  1906,  vol.  ii.,  p.  1554. 

Op.cit. 


194  THE  NATURAL  HISTORY  OF  CANCER 

(c)  Grafting  Experiments  as  between  Animals  of  Different  Species  etc. 

Notwithstanding  alleged  instances  to  the  contrary,  the  transmission  of 
cancer  from  one  animal  to  another  of  a  different  species,  has  never  been 
definitely  proved. 

Doultrelepont x  failed  to  transplant  grafts  of  cancer  from  the  mamma 
of  a  bitch  into  guinea-pigs  and  rabbits  ;  and  most  experimenters  have 
failed  to  transmit  the  so-called  "  cancer  "  of  mice  and  rats  to  other 
animals  of  different  species. 

I  have  previously  referred  to  the  negative  results  of  Dupuytren's  and 
Shattock's  experiments,  of  feeding  dogs  and  other  animals  with  human 
malignant  tumours. 

Here  passing  mention  may  be  made  of  certain  alleged  examples  of 
the  transmission  of  cancer  from  human  beings  to  animals,  or  vice  versd, 
by  accidental  contagion  :  for  instance,  Hyatt  has  reported  the  transfer 
of  melanotic  sarcoma  from  the  horse  to  man  ;  Gross  that  of  cancer  from 
domestic  animals  to  man  ;  Kuhn  the  case  of  a  woman,  who  inoculated 
her  finger  with  cancer  while  tending  a  cancerous  cow  ;  Juergens  the 
transfer  of  epithelioma  from  a  fowl  to  a  man's  finger  ;  Budd  the  case  of 
a  pet  dog,  who  contracted  cancer  of  the  tongue,  from  licking  his  master's 
cancerous  lip  ;  Bosc,  the  transfer  of  epithelioma  from  a  trout — that  had 
been  eaten  raw — to  a  young  man's  tongue,  wounded  at  the  time  by  the 
spines  of  the  fish  etc. 

According  to  Noel,  even  certain  tree  tumours  ("  arboreal  cancers  "), 
may  by  contagion  communicate  the  malady  to  human  beings  and  animals  ; 
while  Behla  considers  that  the  cabbage  parasite  (Plasmodiophora  brassicce) 
is  equally  potent  in  the  same  direction. 

Wasps,  bugs,  fleas,  and  flies,  have  all  been  regarded  as  infective  agents 
in  this  sense  ;  and  Behla  considers  that  the  peculiar  local  distribution  of 
cancer  at  Luckau,  is  due  to  the  agency  of  contagion  conveyed  by  dogs, 
cats,  rats,  mice  etc.,  besides  the  uncooked  cabbages,  radishes,  water- 
cresses  with  other  vegetables,  and  the  dirty  water. 

I  have  mentioned  these  items,  not  that  any  present  credibility  attaches 
to  them,  so  far  as  I  can  see  ;  but  because  they  ought  to  be  in  the  naturalist's 
mind,  when  considering  this  aspect  of  the  subject. 

(d)  The  Transmission  of  Cancer  as  between  Human  Beings. 

If  cancer  could  be  proved  to  be  an  inoculable  contagious  malady, 
the  question  as  to  its  causation  would  be  greatly  simplified,  in  favour  of 
extrinsic  factors  ;  but,  so  far  as  we  have  hitherto  examined  this  question, 
no  reliable  evidence  of  contagion  has  been  forthcoming. 

Interest,  of  course,  centres  especially  as  to  the  evidence  of  contagious- 
ness between  human  beings  ;  and  this  is  the  aspect  of  the  question  to 
which  I  now  propose  to  invite  attention. 

Even  as  far  back  as  the  middle  of  the  seventeenth  century,  there 
were  those  who  believed  that  cancer  was  communicable  by  direct  con- 

1  Arch.  f.  path.  Anat.,  1869,  Bd.  xlv.,  S.  501. 


THE  EXPERIMENTAL  STUDY  OF  CANCER  GENESIS      195 

tagion  ;  and,  in  support  of  this  belief,  the  case  of  a  woman  with  ulcerated 
cancer  of  the  breast,  who  is  said  to  have  communicated  the  disease  to  her 
three  sons  who  slept  with  her,  is  instanced  by  Zacutus  Lusitanus  (1649). 
A  later  author  of  this  period,  Nicolaus  Tulpius  (1672),  in  support  of  the 
same  thesis,  has  related  the  case  of  an  elderly  lady  with  ulcerated  cancer 
of  the  breast,  who  is  also  said  to  have  communicated  the  malady  to  her 
servant  and  nurse.  Even  as  late  as  the  middle  of  the  eighteenth  century, 
cancer  patients  were  refused  admission  into  the  Hotel  Dieu  at  Reims, 
on  account  of  the  supposed  contagiousness  of  the  malady. 

In  opposition  to  these  fanciful  conceptions,  I  can  appeal  to  my  eight 
years'  experience  at  the  Middlesex  Hospital,  where — although  I  was 
daily  in  the  cancer  wards — I  never  noticed  a  single  fact  that  could  possibly 
be  construed  as  evidence  of  the  communicability  of  malignant  disease 
from  one  human  being  to  another  ;  but  I  noticed  many  indications 
which  seemed  clearly  to  imply,  that  the  disease  was  neither  infectious 
nor  contagious.  At  that  time,  the  special  wards  were  packed  with 
patients  in  advanced  stages  of  cancer,  mostly  of  the  breast  and  uterus, 
in  a  state  of  ulceraticji.  There  were  no  day-rooms  for  these  patients  ; 
they  lived  and  died  in  the  same  wards.  No  sooner  was  one  dead,  than 
her  place  was  taken  by  another.  The  crowding  was  great ;  yet,  during 
a  period  of  twenty  years,  not  a  single  instance  is  known  in  which  a  nursing 
sister,  probationer,  nurse,  ward-servant,  surgeon,  student,  or  anyone 
engaged  in  attendance  on  the  cancer  patients,  ever  acquired  the  disease. 
The  nursing-sister  in  charge  held  her  office  for  over  a  quarter  of  a  century, 
but  she  was  never  affected. 

Among  these  cancer  patients  were  many  who  had  been  inadvertently 
admitted,  with  various  chronic  ulcerative  affections  of  a  non-cancerous 
nature  ;  some  of  these  lived  for  years  in  the  cancer  wards,  but  none  of 
them  ever  took  the  disease. 

Many  supposed  examples  of  the  transmission  of  cancer  from  one  human 
being  to  another  have  from  time  to  time  been  recorded  (Budd,1  Guelliot,2 
Bosc,3  Guermonprez,4  Cabot,5  Fabre,6  Behla,7  Boas,8  MacEwen,9  and 
others)  ;  but,  the  evidence  adduced  as  to  contagion  in  these  cases,  is  of 
such  a  flimsy  and  obviously  unreliable  nature,  as  to  absolve  me  from  the 
necessity  of  detailed  refutation. 

On  the  other  hand,  besides  such  items  as  I  have  previously  mentioned, 
there  is  some  strong  evidence  as  to  the  non-contagiousness  of  the  disease 
between  human  beings,  which  I  will  now  proceed  to  relate. 

The  attempts  made  in  Paris  at  the  Hopital  St.  Louis,  early  in  the 
nineteenth  century,  by  Alibert,10  Biett,  and  others,  to  inoculate  them- 

1  For  a  series  of  cases,  vide  the  Lancet,  1887,  vol.  ii.,  pp.  727,  888,  919,  986,  1091, 
1 145,  etc.     I  regard  these  simply  as  highly  exceptional  coincidences. 

2  Gaz.  des  Hdpitauz,  1892,  No.  129,  p.  1209;  also  L'  Union  med.  du  Nord-Est,  1891, 
xv.,  p.  106  et  seq. 

3  "Le  Cancer,"  Paris,  1898. 

*  Butt.  Med.,  March  11,  1896. 

6  Boston  Medical  and  Surgical  Journal,  1901,  vol.  cxliv.,  p.  471. 

6  Thesede  Lyon,  1892. 

7  Deutsche  med.  Woch.,  June  27,  1901. 

8  Verhandl.  d.  XVIII.  Cong.  f.  Med.,  1900,  S.  374. 

9  Glasgow  Medical  Journal,  1886. 

10  "  Description  des  Maladies  de  la  Peau  observees  a  1'Hopital  St.  Louis,"  1806,  p.  118. 

13—2 


196  THE  NATURAL  HISTORY  OF  CANCER 

"/selves  and  their  pupils  with  the  disease,  were  uniformly  unsuccessful. 
In  modern  times,  Senn  *  implanted  the  fresh  pulp  of  a  recently  removed 
cancerous  gland  into  the  subcutaneous  tissue  of  his  forearm,  with  a 
negative  result ;  and,  in  like  manner,  ended  Wickham's  attempt  to  inocu- 
late himself  with  tissue  from  a  case  of  "  Paget's  disease  "  of  the  breast, 
associated  with  cancer. 

Notwithstanding  the  frequency  with  which  surgeons  and  medical 
men  are  exposed  to  contagion,  in  the  ordinary  course  of  their  professional 
duties,  not  a  single  well-authenticated  instance  has  been  recorded,  in 
which  the  disease  has  been  acquired  in  this  way. 

Of  the  thousands  of  persons  habitually  engaged  in  attendance  upon 
the  victims  of  this  disease,  how  few  have  ever  been  similarly  affected  ! 

The  United  States  Census  Report,  for  1900,2  having  shown  a  high 
death-rate  from  cancer,  among  nurses  and  midwives,  as  compared  with 
occupied  females  in  general,  the  attempt  has  been  made  to  utilize  this 
item,  as  evidence  of  contagion  ;  but,  besides  the  need  for  caution  in  dealing 
with  the  statistics  of  this  country  owing  to  their  peculiar  mode  of  col- 
lection etc.,  as  mentioned  in  a  previous  chapter,  which  make  these  data 
particularly  unsuitable  for  determining  a  question  of  this  kind,  it  is  also 
necessary  to  notice  the  great  disparity  in  age  distribution,  which  is  alone 
sufficient  to  entirely  account  for  the  diversity  in  cancer  proclivity,  the 
majority  of  nurses  and  midwives  being  very  much  older  than  most 
domestic  servants,  who  constitute  the  largest  class  of  employed  females  ; 
besides,  the  total  number  of  deaths  from  all  causes  (1,330)  in  this  class, 
and  of  cancer  deaths  (98),  is  much  too  small  to  enable  reliable  death-rates 
to  be  calculated.  In  short,  these  sources  of  fallacy  render  this  item, 
quite  worthless  as  evidence  of  cancer  contagion,  even  if  it  could  other- 
wise be  properly  employed  for  such  a  purpose. 

In  matters  of  this  kind,  naturally  occurring  experiments  are  often  far 
more  conclusive,  than  those  made  under  artificial  conditions,  with  their 
numerous  sources  of  fallacy.  "  Sadly  strange  as  it  may  seem,"  says 
Matthews  Duncan,  "  there  is  scarcely  any  disease,  however  formidable  or 
however  loathsome,  in  spite  of  which  sexual  intercourse  and  conception 
may  not  take  place."  This  is  strikingly  true  of  uterine  cancer,  which  is 
far  more  frequently  complicated  with  pregnancy  than  is  generally  believed 
and,  in  the  earlier  stages  of  the  disease,  no  doubt  the  sexual  appetite  is 
increased,  and  sexual  intercourse  is  of  common  occurrence. 

In  proof  of  this,  it  may  be  mentioned  that  Noble  3  had  no  difficulty 
in  collecting  records  of  166  cases  of  pregnancy  complicated  with  uterine 
cancer,  published  during  the  decennium  1886-1895  ;  and  it  would  be  easy 
to  add  to  this  list.  Cohnstein4  has  reported  a  remarkable  series  of 
cases,  in  which  more  than  a  single  pregnancy  was  known  to  have 
taken  place,  during  the  course  of  uterine  cancer.  I  know  of  instances  of 
.  pregnancy  having  occurred  after  amputation  of  the  cancerous  cervix, 
and  after  curettage  for  the  same. 

1  Journal  of  the  American  Medical  Association,  April  28,  1906,  p.  1255. 

2  Vol.  iii.,  part  i.,  p.  ccxcviii,  etc. 

3  American  Journal  of  Obstetrics,  etc.,  February,  1896,  p.  283. 
*  Arch.  f.  Gyn.,  Bd.  v.,  S.  366. 


THE  EXPERIMENTAL  STUDY  OF  CANCER  GENESIS     197 

Yet,  in  spite  of  these  facts,  I  am  not  aware  of  a  single  well-authenti- 
cated case  of  cancer  of  the  penis  acquired  in  this  way. 

Of  134  men  with  cancer  of  the  penis,  tabulated  by  Demarquay,1  only 
one  had  a  wife  with  uterine  cancer.  Bossi,2  who  has  recently  reinvesti- 
gated  this  important  subject,  has  arrived  at  a  similar  result :  of  180 
husbands  known  to  have  had  marital  relations  with  wives  the  subjects 
of  uterine  cancer,  not  a  single  one  had  acquired  the  disease. 

In  like  manner,  Bayle — many  years  ago — reported  that,  having  had 
under  observation  a  considerable  number  of  men,  who  had  habitually 
maintained  marital  relations  with  wives  known  to  be  affected  with 
uterine  cancer,  not  one  ever  contracted  the  disease. 

The  comparatively  few  cases,  in  which  cancer  of  the  uterus  and  penis 
have  coexisted  in  husband  and  wife  is  so  small,  as  to  deprive  them  of  all 
value  as  evidence  of  contagion.  It  accords  with  this,  that  cancer  of  the 
penis  is  a  rare  affection,  while  uterine  cancer  is  exceedingly  common  ; 
thus,  in  1900,  3,679  women  died  of  uterine  cancer  in  England  and  Wales  ; 
but,  only  100  men  died  of  cancer  of  the  penis. 

Among  the  forty-three  cases  of  this  conjunction  collected  by  Behla 
and  Guelliot  from  various  sources,  is  one  reported  by  Tross,  in  which 
the  penile  disease  is  said  to  have  consisted  of  structures  identical  with 
those  of  the  uterine  malady — glandular  cancer  of  the  cervix.  Referring 
to  this  case,  Dr.  Brand3  says  :  "It  alone  is  sufficient  to  prove  that  trans- 
ference of  cancer  ceUs  occurred — that  cancer  is  therefore  contagious." 
When  such  supreme  importance  is  attached  to  a  particular  case,  it  surely 
is  not  too  much  to  ask,  that  all  the  details  relating  thereto  shall  be  publicly 
set  forth,  and  submitted  for  verification,  to  the  scrutiny  of  some  com- 
petent professional  tribunal ;  in  the  absence  of  any  such  details  and 
impartial  scrutiny,  I  shall  perhaps  be  pardoned  if  I  decline  to  accept 
the  interpretation  of  the  histological  appearances  in  the  sense  alleged. 

Again,  the  children  of  cancerous  mothers  do  not  acquire  the  disease, 
even  when  the  placenta,  uterus,  or  other  part  of  the  genital  tract  is  the 
seat  of  the  malady.  Moreover,  mothers  with  cancer  of  the  breast  have 
often  suckled  their  infants  with  the  diseased  organ,  without  transmitting 
the  malady  to  their  offspring. 

Thus,  there  is  every  reason  to  believe  that  cancer  cannot  be  trans- 
mitted from  one  human  being  to  another  ;  and  that  it  is,  in  fact,  essentially 
a  non-contagious  malady. 

(e)  Auto-Implantation. 

Several  instances  of  the  apparently  successful  auto-implantation  of 
malignant  tumours,  in  human  beings,  have  now  been  reported. 

Hahn,4  for  instance,  having  removed  some  small  cancerous  nodules 
from  the  skin  of  a  woman  with  recurrent  mammary  cancer,  implanted 
them  into  small  wounds  made  in  the  skin  of  the  mammary  region,  on  the 
opposite  side  of  the  body.  In  the  course  of  two  months,  these  grafts 

1  "  Mai.  Chir.  du  Penis,"  1876. 

2  Oaz.  degli  Osped.,  April  13,  1902. 

3  Quarterly  Medical  Journal,  May,  1903. 

4  Berlin,  klin.  Woch.,  1888,  Xo.  21,  S.  413. 


198  THE  NATURAL  HISTORY  OF  CANCER 

increased  to  the  size  of  peas  ;  and,  when  the  patient  died  with  general 
metastases  some  weeks  later,  they  were  as  large  as  cherries — their  histo- 
logical  structure  resembling  that  of  the  primary  breast  tumour. 

Cornil  *  has  reported  two  similar  cases.  In  one  of  these  a  fragment  of 
cancer  (6piiheliome  tubuU),  taken  from  the  recently  removed  breast  of 
a  woman,  was  implanted  into  the  opposite  breast ;  where,  in  the  course 
of  several  weeks,  it  grew  into  a  small  tumour.  In  the  other  case,  a  fibro- 
spindle-celled  sarcoma  having  been  removed  from  the  female  breast,  a 
fragment  of  this  tumour  was  implanted  into  the  opposite  breast ;  where, 
in  the  course  of  two  months,  it  attained  the  size  of  an  almond.  The 
implanted  tumour  was  then  excised  ;  and,  histologically  examined,  it 
proved  to  be  of  the  same  structure  as  the  original. 

At  least  two  other  surgeons  are  said  to  have  repeated  these  experi- 
ments, with  similar  results. 

If  we  accept  this  evidence  as  conclusive,  what  has  been  accomplished 
amounts  to  the  artificial  production  of  metastasis. 

In  a  somewhat  similar  experiment  by  Senn,2  in  which  a  fragment  cut 
out  from  a  cutaneous  cancer  of  a  man's  leg,  was  inserted  into  another 
part  of  the  same  leg,  no  growth  subsequently  ensued  ;  and,  by  the  end  of 
a  month,  all  traces  of  the  graft  had  completely  disappeared. 

I  have  found  very  few  experiments  on  record,  as  to  the  auto -implanta- 
tion of  cancer  in  the  lower  animals  :  Senn's  3  attempts  on  a  dog,  affected 
with  sarcoma  of  the  lower  jaw,  failed  ;  but,  with  the  so-called  "  cancer  " 
of  rats  and  mice,  successful  auto-implantations  have  been  made. 

Some  weighty  items  of  evidence  as  to  the  auto-inoculability  of  cancer 
come  from  clinical  sources. 

In  a  considerable  number  of  cases  it  has  been  observed,  that  when 
cancerous  growths  have  remained  for  some  time  in  contact  with  eroded, 
epithelial-covered  surfaces,  the  latter  have  at  length  become  cancerous, 
as  if  by  direct  implantation. 

Cripps  4  has  related  the  case  of  a  woman,  with  extensive  cancerous 
ulceration  of  the  left  mammary  region  ;  who,  being  unable  to  put  on  any 
dress,  had  kept  her  arm — bent  at  a  right  angle — in  constant  contact 
with  the  disease  for  several  months.  In  consequence  of  this,  the  skin 
in  the  vicinity  of  the  elbow  became  the  seat  of  a  cancerous  ulcer,  several 
inches  in  diameter. 

A  somewhat  similar  case  has  been  previously  recorded  by  De  Morgan.5 

He  says,  "  My  colleague,  Mr.  Shaw,  attended  a  woman  whose  pendu- 
lous breast — the  seat  at  its  most  dependent  part  of  ulcerated  cancer — 
rubbed  against  the  skin  of  the  thorax.  At  the  point  of  contact,  a  circular 
patch  of  cancerous  ulceration  (the  size  of  a  florin)  took  place,  the 
intervening  skin  between  this  and  the  fold  of  the  mamma  remaining 
healthy." 

A.  Williams,6  in  a  woman  aged  sixty,  has  reported  the  spread  by 

1  Butt,  de  I'Acad.  de  Med.,  1891,  No.  25  ;  also  Le,  Progres  Med.,  1888,  Nos.  21  and  27. 

2  "Surgical  Bacteriology,"  1889,  p.  262. 

3  Op.  cit.,  p.  261. 

4  Transactions  of  the  Pathological  Society,  London,  1881,  vol.  xxxii.,  p.  111. 
"  On  the  Origin  of  Cancer,"  London,  1872. 

6  British  Medical  Journal,  1887,  vol.  ii.,  p.  1369. 


THE  EXPERIMENTAL  STUDY  OF  CANCER  GENESIS      199 

"  contact  infection,"  of  an  ulcerating  cutaneous  epithelioma  of  the  inner 
part  of  one  thigh,  to  the  corresponding  part  of  the  opposite  thigh. 

Examples  of  the  spread  of  cancer  by  "  contact  implantation,"  from 
the  uterus  to  the  vagina,  have  been  related  by  Thorn,1  Czempin,2  Fischer,3 
Russell,4  and  others. 

One  of  Thorn's  patients,  a  multipara  aged  forty-six — whose  uterus 
had  been  deflected  to  the  right,  where  it  had  become  fixed  in  its  faulty 
position  by  adhesions — subsequently  developed  cancerous  "  cauliflower 
excrescence  "  of  the  portio.  Owing  to  the  faulty  position  of  the  uterus, 
the  diseased  portio  was  constantly  in  contact  with  the  left  side  of  the 
vagina,  at  a  considerable  distance  from  the  fornix.  In  this  position 
papillary  cancer  developed,  which  fitted  the  similar  growth  on  the 
portio,  "  like  a  saucepan-lid."  Elsewhere  the  vagina  was  free  from 
disease. 

Niebergall,  Winter,  Pfannenstiel  and  Leopold  have  described  cases, 
in  which  the  primary  outbreak  of  the  disease  in  the  corpus  uteri,  had 
been  followed  by  the  appearance  of  similar  disease  in  the  cervix  ;  which 
they  ascribe  to  inoculation,  by  contact  with  the  primary  cancerous 
polyp,  or  with  debris  given  off  from  it. 

In  like  manner,  instances  have  been  noted  by  Hamburger,5  Walter 
and  others,  of  the  spread  of  cancer  from  one  vulva  to  the  other,  both  the 
tumours  being  of  the  same  histological  structure. 

In  various  other  parts  of  the  body,  facts  of  similar  import  have  been 
reported,  e.g.,  from  one  lip  to  another  (Bergmann),  from  one  vocal  cord 
to  another,  from  one  eyelid  to  another  (Vennemann),  from  the  tongue 
to  the  adjacent  cheek  (Liicke),  from  the  visceral  to  the  parietal  pleura, 
and  likewise  from  the  visceral  to  the  parietal  peritoneum  etc. 

I  have  seen  several  examples  of  this  kind,  especially  in  the  mouth  and 
bladder. 

Klebs6  has  met  with  instances  in  which  cancer  of  one  part  of  the 
alimentary  tract,  has  been  followed  by  the  development  of  cancerous 
nodules  of  similar  structure  at  other  parts  lower  down,  as  if  by  the  im- 
plantation there  of  detached  fragments  ;  e.g.,  (a)  ulcerated  epithelioma 
of  the  oesophagus,  with  two  small  nodules  of  similar  structure  below  the 
cardia  ;  (6)  ulcerated  epithelioma  of  the  mouth,  with  a  tumour  of  similar 
structure  in  the  large  curvature  of  the  stomach  ;  (c)  epithelioma  of  the 
dorsum  of  the  tongue,  with  a  similar  tumour  in  the  large  curvature  of  the 
stomach. 

Fiitterer7  has  lately  published  another  case  of  this  kind,  and  refers 
to  six  others. 

Moxon  8  and  Ebse  9  have  described  the  spread  of  the  disease  from  the- 
trachea  to  the  lungs,  in  a  similar  way  ;  while  Dickinson  saw  numerous 
discrete  growths  form  in  the  peritoneum,  in  consequence  of  the  rupture- 
of  a  cancerous  lumbar  gland,  which  shed  numerous  detached  particles 

Cent.  }.  Qyn.,  No.  10,  1894.  2  Zzits.  f.  Oeb.  u.  Qyn.,  Bd.  xvi.,  Heft  1. 

Cent.  f.  Qyn.,  1891,  S.  549.  *  American  Journal  of  Obstetrics,  etc.,  vol.  i.,  p.  293, 

Med.-chir.  Rundschau,  1892,  No.  12. 

Handb.  d.  path.  Anat.,  Bd.  i.,  S.  190.  7  Medicine,,  1902,  vol.  viii.,  p.  177. 

Transactions  of  the  Pathological  Society,  London,  vol.  xx.,  p.  18. 

Cent.  f.  CUr.,  1884,  No.  48  (cited  by  Kraske). 


200  THE  NATURAL  HISTORY  OF  CANCER 

into  the  peritoneal  cavity.  Schenk  has  seen  perforated  gastric  cancer 
spread  in  this  way  to  the  ovaries  and  uterus. 

Another  important  class  of  cases,  in  which  implantation  plays  a  leading 
part,  comprises  what  I  am  in  the  habit  of  calling  post- operative  cancers. 

Thus,  Courtin,1  Reinecke2  and  others,  have  noted  the  frequency 
with  which,  after  tapping  for  ascites  due  to  cancerous  disease,  the  wound 
track  itself,  became  cancerous  ;  as  if  through  implantation  in  it  of  can- 
cerous elements,  conveyed  there  by  the  ascitic  fluid. 

Nicaise  has  also  seen  sarcoma  supervene  in  the  track  of  a  punctured 
wound,  made  through  the  abdominal  wall,  into  a  uterine  sarcoma,  under 
the  supposition  that  it  was  a  cyst. 

After  the  extirpation  of  malignant  tumours,  the  resulting  wound  may 
not  infrequently  be  grafted  with  the  disease  in  this  way ;  thus  Schopf  3 
reports  that,  having  had  to  make  lateral  incisions  into  the  vagina  and 
vulva,  during  the  course  of  vaginal  hysterectomy  for  cancer  of  the  uterus, 
these  incisions  subsequently  became  cancerous,  as  if  from  contact  infec- 
tion. Leopold  and  others  have  had  similar  experiences. 

In  other  parts  of  the  body  the  same  thing  has  often  been  noted ; 
thus,  Lawrie  4  has  described  a  case  in  which,  during  exploratory  lapar- 
otomy  for  cancer  of  the  sigmoid  colon,  he  removed  a  ruptured  can- 
cerous gland,  with  his  fingers  ;  fourteen  months  later  a  cancerous  nodule 
appeared  in  the  upper  part  of  the  laparotomy  scar,  owing  to  some  fragment 
of  the  cancerous  gland  having  been  implanted  there  during  extraction.5 

The  by  no  means  rare  occurrence  of  this  kind  of  accident,  after  supra- 
vaginal  amputation  of  the  cancerous  uterus  by  the  abdominal  route,  and 
after  many  abdominal  operations,  is,  I  think,  riow  beginning  to  be 
generally  recognized. 

Indeed,  there  are  good  reasons  for  believing,  that  eroded  surfaces  may 
be  infected  through  contact  even  with  the  discharge  from  cancerous 
ulcers  etc.  ;  and  many  surgeons  now  admit  the  traumatic  dissemination 
of  the  disease,  through  the  inoculation  of  wounds  by  the  escape  of  "  cancer 
juice  "  during  operations. 

Hence,  care  should  be  taken  to  avoid  cutting  into  malignant  neo- 
plasms during  their  removal ;  for,  such  is  the  great  tenacity  of  life  and  the 
wonderful  proliferative  power,  of  even  the  most  diminutive  fragments  of 
cancer,  that  when  left  behind  they  only  too  often  constitute  fresh 
centres  of  disease. 

In  view  of  such  considerations  as  the  foregoing,  even  the  extraordinary 
examples  of  auto -inoculation  reported  by  Schimmelbusch  and  Kaufmann, 
cannot  be  summarily  dismissed  as  being  altogether  improbable  :  the 
former  states  that  a  man  who  was  in  the  habit  of  handling  his  cancerous 
ear,  transmitted  the  disease  to  his  lip,  through  the  medium  of  his  finger- 
nails ;  while  the  latter  relates  the  case  of  a  man  with  epithelioma  of  the 
hand,  who  conveyed  the  disease  to  his  eyelid,  by  continuously  rubbing 
the  part  with  the  diseased  hand. 

1  C.  R.  7"*..  Cong,  de  Chir.  Francaise,  1895. 

2  Arch.  /.  path.  Anat.,  1870,  Bd.  li.,  S.  391.  3   Wien.  med.  Woch.,  1891,  No.  45. 

4  British  Medical  Journal,  1906,  vol.  i.,  p.  198. 

5  For  other  instances  of  this  kind  vide  ibid.,  1907.  vol.  ii..  p.  255  (Butlin) ;  and  Lancet, 
1907,  vol.  ii.,  p.  1311  (Ryall). 


CHAPTER  IX 

CANCER  AND  TUMOUR  GROWTH  IN  RELATION  TO  GROWTH 
IN  GENERAL 

THE  genesis  of  tumour  germs,  and  their  growth,  are  problems  that 
require  separate  consideration. 

In  a  previous  chapter,  comparing  tumour  germs  with  ova,  I  insisted, 
with  reference  to  their  origin,  that  just  as  cells  embedded  in  the  stroma 
of  an  ovarium  become  ova  by  excessive  growth  at  the  expense  of  adjacent 
nutritive  materials,  which  they  divert  from  other  cells  ;  so  it  may  be 
inferred  that  those  cells  which  originate  tumours,  become  different  from 
their  congeners' in  a  similar  way. 

It  will,  I  think,  aid  us  in  arriving  at  correct  ideas  as  to  the  nature  and 
conditions  of  tumour  growth,  if  we  extend  our  analogy,  so  as  to  embrace 
also  this  part  of  the  problem  ;  that  is  to  say,  by  comparing  tumour  growth 
with  the  growth  from  the  ovum — for  no  doubt  all  the  attributes  of  tumours 
are  but  the  consequences  of  their  modes  of  growth. 


Of  Growth  in  General. 

But,  before  entering  on  this  matter,  it  seems  desirable  briefly  to  survey 
the  subject  of  growth  in  general. 

At  the  outset  it  must  be  mentioned,  that  growth  is  always  accompanied 
by  marked  changes  of  form  ;  and,  moreover,  for  each  kind  of  being  and 
for  each  part,  growth  has  a  determinate  limit.  With  regard  to  the 
various  parts  and  organs,  their  growth  in  the  course  of  ontogeny  is  by 
no  means  uniform  ;  for,  while  in  some  the  process  ceases,  in  others  it  is 
renewed  with  fresh  vigour.  Indeed,  the  ontogeny  of  every  higher  organism 
presents  a  twofold  progress,  proceeding  pari  passu.  On  the  one  hand, 
there  is  continuous  perfecting  of  bodily  structure  by  increasing  histo- 
logical  and  morphological  differentiation,  whence  the  various  tissues  and 
organs  result ;  and,  on  the  other  hand,  there  is  continual  transition  from 
lower  and  more  general,  to  higher  and  more  specific  types  of  organization. 

The  most  remarkable  of  these  morphological  manifestations  of  growth 
take  place  in  young  animals,  especially  during  the  embryonic  period ; 
but,  changes  of  this  kind  also  occur  in  post-natal  life,  even  in  mankind 
and  the  highest  animals,  of  which  examples  are  seen  in  dentition,  puberty, 
pregnancy,  lactation  etc. 

The  earliest  products  of  the  histological  differentiation  of  the 
embryonic  epiblast  and  hypoblast,  are  layers  of  the  epithelial  cells  which 

201 


202  THE  NATURAL  HISTORY  OF  CANCER 

function  as  the  primitive  organs.  The  organs  of  the  adult  are  evolved  from 
these  layers  by  further  differentiations  :  certain  of  their  cells  become  as 
it  were  the  germs,  whence  these  organs  bud  forth  in  a  definite  and  orderly 
manner,  the  essence  of  the  process  being  that  at  certain  points  more 
intense  cell  proliferation  sets  in  than  elsewhere.  Solid  bud-like  processes  of 
proliferous  cells  thus  arise  ;  which,  as  they  increase,  grow  into  the  adjacent 
tissues.  The  further  development  of  such  a  bud  or  initial  cellular  mass 
may  be  either  continuous  or  discontinuous  :  it  may  spread  as  ingrowth, 
outgrowth,  or  sometimes  as  both,  the  ultimate  form  of  the  resulting 
organ  being  only  gradually  attained  through  subsequent  successive 
modifications. 

In  these  various  types  of  normal  epithelial  new  formations,  we  see  the 
prototypes  of  corresponding  pathological  new  formations.  In  all  cases, 
these  morbid  productions  seem  to  result  from  a  modified,  super-induced 
repetition  of  some  portion  of  the  normal  developmental  process  of  the 
affected  part  or  its  vicinity.  Just  as  there  are  good  reasons  for  believing 
that  the  primordial  starting-point  of  every  organ  is  a  single  cell ;  so, 
likewise,  we  may  conclude  that  every  tumour  probably  has  a  similar 
origin.  This  need  excite  no  surprise,  when  we  recollect  the  wonderful 
reproductive  properties  of  cells. 

Under  normal  conditions,  growth  proceeds  in  a  regular  and  orderly 
manner,  in  accordance  with  the  specific  hereditary  tendency  of  the 
whole  ;  and,  just  as  the  great  problem  of  physiology  is  to  explain  this 
orderly  sequence,  so  the  great  problem  of  tumour  pathology  is  to  explain 
how,  under  abnormal  conditions,  the  disordered  rhythm  of  growth  is 
produced  of  which  tumours  are  the  outcome. 


Of  Growth  in  Cells. 

Ever  since  the  establishment  of  the  cell  theory,  it  has  become  clearer 
and  even  clearer,  that  the  solution  of  all  biological  problems — including 
those  of  tumour  formation — must  ultimately  be  sought  in  cell  life  and 
cell  processes.  We  will  therefore  proceed  with  our  task  by  studying 
growth  in  the  individual  cell.  As  the  one  really  essential,  universal, 
physiological  property  common  to  all  living  things,  growth  is  a  pheno- 
menon of  the  greatest  importance.  To  our  senses  cell  growth  manifests 
itself  as  a  rhythmic  process,  in  which  increase  of  size  alternates  with 
increase  of  number  or  multiplication  ;  and,  at  the  same  time,  there  is 
concomitant  structural  differentiation  of  the  growing  unit,  that  is  to 
say,  change  from  the  general  to  the  special.  This  change  is  commonly 
termed  "  development,"  and  is  often  held  to  be  fundamentally  distinct 
from  growth.  It  may  be  said  that  growth  is  due  to  the  tendency  of  like 
units  to  unite,  and  of  unlike  units  to  separate  ;  or,  as  Spencer  has  it : 
"  Growth  is  an  integration  with  the  organism  of  such  environing  materials, 
as  are  of  like  nature  with  it."  All  living  things  grow  by  taking  into  their 
substance  new  particles,  which  they  dissolve  and  convert  into  new  living 
matter.  This  latter,  the  physical  basis  of  life,  is  the  nitrogenous  carbon 
compound — protoplasm  ;  of  which  it  may  be  said,  that  its  molecules  are 


CANCER  AND  TUMOUR  GROWTH  203 

of  such  kinds  and  so  compounded,  as  easily  to  admit  of  rearrangement. 
Thus,  its  constitution  specially  fits  it  to  receive  and  produce  the  internal 
changes,  required  to  balance  the  external  changes,  the  continuous  adjust- 
ment of  which — according  to  Spencer — constitutes  life. 

The  young  cell  is  small ;  it  increases  in  size,  through  the  assimilation 
by  its  elements  of  a  larger  quantity  of  nutritive  materials,  than  is  required 
for  the  repair  of  waste  and  maintenance  (anabolism).  Having  thus 
attained  a  certain  normal  size,  which  varies  for  different  kinds  of  cells, 
this  excess  of  nutritive  materials  is  dissipated  and  used  up  for  the 
production  of  new  cells  (katabolism)  ;  that  is  to  say,  there  is  reproduc- 
tion, multiplication,  or  growth  of  the  cell  beyond  its  individual  limit  of 
size. 

As  to  the  real  nature  of  the  force  which  determines  the  limit  of  cell 
growth  and  its  form,  we  can  only  surmise  that  it  has  some  similitude  to 
crystal  formation.  Just  as,  in  the  latter,  we  see  that  the  whole  aggregate 
exerts  a  force,  which  constrains  the  newly  integrated  units  to  take  up  a 
certain  definite  form  ;  so,  it  may  be  assumed,  the  rearrangements  of 
organic  units  are  determined  in  a  somewhat  similar  way.  This  hypo- 
thetical property,  as  to  the  real  nature  of  which  we  are  in  both  cases 
ignorant,  is  called  polarity.  Thus  regarded,  polarity  may  be  defined 
as  the  resultant  of  the  physico-chemical  forces  which  determine  mole- 
cular arrangement ;  hence,  in  the  evolution  of  organic  form,  the  polarity 
of  protoplasm  is  a  very  important  factor. 

It  is  also  noteworthy,  that  the  size  and  qualities  of  particular  cells 
depend  chiefly  upon  heredity,  that  is  to  say,  upon  inherent  potentialities 
of  parental  origin. 

In  every  act  of  reproduction,  a  certain  quantity  of  protoplasm  is 
transferred  from  the  producing  to  the  produced  cell ;  and,  along  with 
it,  the  molecular  motion  peculiar  to  the  parental  unit.  The  phenomena 
of  heredity  are,  in  fact,  dependent  upon  this  material  continuity  and 
partial  identity,  of  the  producing  and  produced  organisms. 

It  is  generally  believed  that  each  cell,  after  its  formation,  begins  at 
first  to  grow  slowly,  then  reaches  its  greatest  rapidity  of  growth  ;  and 
ultimately  growth  declines,  until  at  last  it  ceases  :  thus,  there  is  a  wave- 
like  rhythm,  with  periods  of  increase,  maturity  and  decline.  According 
to  Minot,1  however,  the  rate  and  power  of  growth  steadily  decrease,  from 
the  beginning  to  the  end  of  life.  If  we  accept  this  view,  it  follows  that 
stoppage  of  growth  is  not  due  to  the  attainment  of  maturity,  but  is  merely 
the  final  term  of  a  long  series  of  losses  ;  and,  pushing  this  argument  to 
its  logical  conclusion,  Minot  maintains  that  loss  of  vital  force — "  senes- 
cence " — is  the  stimulus  which  inaugurates  discontinuous  growth  or 
proliferation. 

In  these  ways  then  the  form  and  substance  of  cells  are  altered,  and 
at  the  same  time  their  physiological  properties  are  altered,  so  that  new 
relations  are  established. 

All  sorts  and  conditions  of  growth  in  the  end,  will  be  found  to  depend 
upon  the  molecular  processes  of  nutrition — understanding  by  this  term 
the  whole  of  the  material  changes  wrought  in  the  organism,  through  the 
1  "  Reference  Handbook  of  the  Medical  Sciences,"  1889,  vol.  iii.,  p.  398. 


204  THE  NATURAL  HISTORY  OF  CANCER 

influence  of  the  surrounding  outer  world.  These  many  complicated 
conditions  never  being  absolutely  identical  for  any  two  cells,  it  follows 
that  variability  is  a  universal  property  of  all  cells.  Thus,  change  of 
nutrition  is  unquestionably  the  true  cause  of  all  morphological  variation  ; 
which,  according  to  Virchow,  always  has  its  foundation  in  a  pathological 
accident.  By  disease,  in  fact,  we  merely  imply  a  phase  of  life,  whose 
manifestations  deviate  in  some  way  from  the  normal,  owing  to  perturba- 
tions caused  by  changed  or  abnormal  conditions  of  existence.  Thus, 
our  conception  of  disease  is  a  purely  physiological  conception,  which 
recognizes  the  identity  of  the  laws  governing  physiological  and  patho- 
logical processes  ;  and  traces  the  diversity  between  the  two,  to  differences 
in  the  conditions  under  which  the  organic  forces  and  substances  operate. 
A  necessary  outcome  of  this  conception  of  disease  is,  that  every  patho- 
logical process  has  its  physiological  prototype — a  great  principle  of 
modern  pathology  the  full  significance  of  which  is,  even  now,  far  from 
being  adequately  recognized. 

In  any  given  case,  it  is  impossible  to  say  where  health  ends  and  disease 
begins  ;  thus,  no  one  can  determine  where  what  are  called  normal  morpho- 
logical variations  end,  and  where  cancer  and  tumour  formations  begin. 
All  that  we  can  say  is,  that  when  structural  or  functional  changes  are 
hurtful,  they  belong  to  the  province  of  pathology.  The  study  of  healthy 
processes  must,  therefore,  necessarily  precede  that  of  the  study  of  the 
phenomena  of  disease. 

Had  the  pathologists  of  half  a  century  ago,  been  imbued  with  more 
adequate  knowledge  and  understanding  of  the  fundamental  principles 
and  methods  of  biology,  our  present  knowledge  of  tumour  pathogenesis 
would  be  much  in  advance  of  the  standard  actually  attained  ;  for,  even 
now,  it  is  chiefly  owing  to  this  kind  of  defect,  that  so  many  modern 
endeavours  miscarry. 

Other  things  being  equal,  growth  varies  according  to  the  surplus  of 
nutrition  over  expenditure  ;  and  it  is  unlimited  or  has  a  definite  limit, 
according  as  this  surplus  does  or  does  not  progressingly  decrease. 

Why  should  growth  tend  in  the  direction  of  cell  proliferation,  rather 
than  to  the  production  of  large  unicellular  aggregates  ?  We  must  seek 
the  answer  to  this  question,  in  the  conditions  of  molecular  cohesion  in 
protoplasm.  In  all  cases  the  process  is  evidently  one  of  disintegration  ; 
and,  as  such,  opposed  to  that  integration  which  constitutes  the  individual. 
According  to  C.  F.  Wolff,  there  is  a  certain  relation  between  the  commence- 
ment of  the  process  and  declining  growth.  For  cell  multiplication  does 
not  take  place  while  the  parental  individual  is  growing  rapidly,  that  is 
to  say,  while  the  process  of  growth  greatly  exceeds  the  opposing  forces  ; 
but  it  begins,  when  nutrition  is  nearly  equalled  by  expenditure. 

It  is  customary  to  speak  of  both  protoplasm  and  nucleus,  as  the 
essential  constituents  of  a  typical  cell ;  and  to  these  modern  cytologists 
add  the  centrosome.  It  must,  however,  be  distinctly  understood,  that 
all  the  parts  of  the  cell  are  knit  together  in  organic  unity.  Most  cytolo- 
gists now  regard  the  nucleus  as  the  most  important  constituent  of  the 
cell ;  and,  to  this  organ,  they  specially  attribute  its  maintenance  and 
multiplication  as  a  living  entity.  Thus,  the  nucleus  presides  over  the 


CANCER  AND  TUMOUR  GROWTH  205 

constructive  metabolism  of  the  cell,  being  specially  concerned  in  the 
formative  processes  involved  in  all  kinds  of  physiological  and  patho- 
logical growth  and  development ;  and,  it  is  through  the  nucleus,  that 
specific  qualities  are  transmitted  from  cell  to  cell,  by  heredity.  The 
earliest  manifestations  of  all  kinds  of  ceU  growth  and  multiplication  are, 
therefore,  to  be  looked  for  in  nuclear  changes.  Young  cells  generally 
have  relatively  large  nuclei,  surrounded  by  scanty  protoplasm. 

In  support  of  these  claims  for  nuclear  pre-eminence,  it  may  be  men- 
tioned that  Griiber,  Nussbaum  and  others,  have  shown  that  when  uni- 
cellular organisms  are  artificially  divided,  only  those  fragments  which 
comprise  nuclear  elements,  are  capable  of  growing  and  multiplying — the 
others  gradually  perish.1 

The  centrosome  is  a  minute  body,  or  pair  of  bodies,  which  lies  in  the 
cytoplasm  near  the  nucleus,  surrounded  by  the  rounded  attraction 
sphere  (archoplasm),  or  by  a  cytoplasmic  radiating  aster.  It  is  regarded 
by  Boveri  and  other  cytologists  as  the  special  organ  of  proliferation  ; 
and,  therefore,  the  dynamic  centre  of  the  cell.  The  precise  status  of  the 
centrosome  is,  however,  still  sub  judice. 

Growth  being  an  integration  with  the  organism  of  such  environing 
matters  as  are  of  like  nature  with  it,  is  necessarily  dependent  upon  the 
available  supply  of  such  materials  :  of  these  the  most  essential  is  water, 
for  it  is  certain  that  living  things  cannot  grow  without  it,  however  abun- 
dant the  other  requisites  may  be.  Light,  heat,  and  nutriment  are  als» 
important  factors.  The  quality  and  quantity  of  nutritive  material  at 
the  disposal  of  a  cell,  has  a  profound  influence  upon  its  behaviour. 

In  cell  proliferation,  to  which  all  organic  units  are  inherently  prone, 
the  occurrence  and  nature  of  the  process — whether  by  agamogenesis, 
gamogenesis,  or  alternation  of  generations — is  determined  by  the  con- 
ditions of  nutrition.  Impregnation  may  be  regarded,  as  merely  one  of 
the  various  conditions,  which  affect  the  process  :  the  influence  of  the  male 
element  on  the  germ-cell,  as  Caspar  Friedrich  Wolff  long  ago  suggested, 
being  comparable  to  that  of  a  kind  of  nutriment. 

There  are  good  reasons  for  believing  that,  in  unicellular  forms,  life 
runs  in  cycles  of  asexual  cell  divisions,  which  are  strictly  limited — the 
separate  cells  of  one  such  cycle  being  collectively  analogous  to  the  entire 
body  of  a  multicellular  organism.  Each  of  these  cycles  begins  and  ends 
with  an  act  of  conjugation.  In  support  of  this  conclusion,  Maupas' 
researches  on  infusorians  may  be  instanced.  By  following  for  a  long 
period  the  life-history  of  various  species,  through  the  entire  cycle  of  their 
existence,  he  showed  that  after  a  time  the  processes  of  growth  and 
development  in  these  unicellular  animals,  tended  to  come  to  an  end,  owing 
to  4i  senescence  ";  and  this  defect  could  only  be  overcome  by  conjugation. 
Thus,  having  isolated  an  infusorian,  which  in  the  course  of  several  months 
produced  agamically  215  generations,  Maupas  found  that  the  individual 
cells  were  exhausted  ;  and,  the  return  to  their  normal  standard  of  vitality 
could  only  be  effected,  after  conjugation  with  an  alien  strain.  In  the  X 

1  It  has,  however,  recently  been  demonstrated  by  Boveri  and  Delage,  that  denucleated 
eggs  of  the  sea-urchin  can  be  fertilized,  when  they  give  rise  to  normal  gastrulae  and  larvae  ;. 
so  that,  if  these  experiments  are  substantiated,  the  nucleus  is  not  the  sole  vehicle  of 
heredity. 


206  THE  NATURAL  HISTORY  OF  CANCER 

absence  of  this  union,  the  race  died  out.  Thus  conjugation  was  shown  to 
be  requisite,  for  restoring  to  the  cells  their  exhausted  vitality — union  of 
the  nuclei  of  the  conjugating  cells  being  an  essential  part  of  the  process. 
In  this  way,  the  physical  admixture  of  protoplasmic  matter  from  two 
different  sources,  is  ensured.  The  new  cell  thus  produced  must  be 
regarded  as  an  entirely  new  formation,  since  in  it  the  characters  of  both 
the  conjugating  cells  are  potential. 

Many  biologists  have  proved  that  abundant  nutrition  favours  asexual 
proliferation  :  thus  Zacharias  found  that  planarians  multiplied  rapidly 
in  this  way,  when  copiously  supplied  with  food  ;  but,  when  the  latter 
was  withheld  or  greatly  reduced,  asexual  multiplication  ceased.  In  like 
manner  Maupas,  having  restricted  infusorians  to  vegetarian  diet,  noted 
great  diminution  in  the  rate  of  the  asexual  cell  divisions. 


Growth  in  Multicellular  Organisms. 

Just  as  the  constituent  elements  of  single  cells,  together  with  their 
various  differentiated  parts,  e.g.,  nucleus,  centrosome,  etc.,  are  knit 
together  into  an  organic  unity  ;  so,  in  like  manner,  the  constituent  cells 
of  the  multicellular  organism,  are  also  integrated  and  co-ordinated  into 
one  organic  whole,  notwithstanding  the  structural  and  functional  differen- 
tiations of  their  constituent  cells.  In  such  organisms,  the  tissue  cells 
can  only  be  regarded,  in  a  restricted  sense,  as  being  independent  units  ; 
for  their  autonomy  is  subservient,  in  greater  or  lesser  degree,  to  the 
requirements  of  the  whole  aggregate. 

There  can,  I  think,  be  no  doubt  that  the  activities  of  the  local  cells 
are  largely  controlled  by  the  totality  of  the  forces  which  determine  the 
form  of  the  whole  organism  ;  and  the  best  conception  as  to  the  nature  of 
this  force  that  biologists  have  yet  evolved,  appears  to  me  to  be  the  one 
formulated  by  Spencer,  which  represents  it  as  being  akin  to  the  force 
which  determines  the  integration  of  crystals.  The  tissue  cells  must 
thus  be  regarded  as  local  centres  of  a  formative  power,  pervading  the 
growing  mass  of  the  whole  aggregate.  If,  during  the  later  stages  of 
development,  some  cells  acquire  a  disproportionately  high  degree  of 
physiological  independence,  this  may  be  regarded  as  a  secondary  con- 
sequence of  development,  by  virtue  of  which  these  cells  become  more  or 
less  emancipated  from  the  general  control. 

The  researches  of  Carnoy  and  other  cytologists  give  some  warrant  for 
this  conception  ;  for,  they  have  demonstrated  that  the  constituent  cells 
of  multicellular  organisms,  are  knit  together  by  protoplasmic  cell- 
bridges  (ponts  intercellulaires),  in  which  cell  membrane,  protoplasm, 
and  sometimes  even  nuclear  filaments,  are  involved  (Ide).  Hence  it 
may  be  inferred,  that  besides  serving  as  nutritive  channels,  these  bridges 
also  transmit  physiological  impulses  from  cell  to  cell. 

In  view  of  these  discoveries,  it  seems  probable  that  Heitzmann  was 
not  far  from  the  right  track,  when  he  described  the  metazoan  organism 
as  a  kind  of  huge  protoplasmic  syncytium,  of  which  the  constituent  cells 
are  merely  nodal  points. 


CANCER  AND  TUMOUR  GROWTH  207 

It  is  generally  admitted  that  the  growth  of  multicellular  organisms 
depends  chiefly  upon  the  multiplication  of  cells,  and  only  to  a  slight 
degree  upon  the  increase  in  size  of  individual  cells  ;  hence,  it  seems  clear, 
that  the  amount  of  growth  is  determined  by  limitation  of  the  process  by 
which  cells  are  increased,  both  as  regards  number  and  rate  of  multipli- 
cation. 

The  question  of  the  causative  factors  of  cell  growth  and  multiplica- 
tion, is  the  most  fundamental  and  important  in  the  whole  range  of 
biology— physiological  as  well  as  pathological — and,  in  the  proper  under- 
standing of  this  question,  the  mystery  of  cancer  and  tumour  formation 
undoubtedly  concentres. 

Biologists  have  long  been  aware  of  the  fact,  that  the  unfertilized 
ova  of  many  animals  are  capable  of  a  certain  amount  of  developmental 
exegesis  ;  although,  after  a  time,  the  process  usually  ceases  spontaneously, 
and  the  cells  degenerate  and  are  absorbed. 

In  certain  exceptional  cases,  however,  the  ontological  exegesis  of 
the  egg  may  proceed  to  its  destination  without  fertilization  ;  and,  whether 
the  development  is  by  gamogenesis  or  by  agamogenesis,  seems  often  to 
depend  chiefly  upon  the  conditions  of  nutrition. 

In  this  connexion  the  phenomena  of  parthenogenesis  are  of  much 
interest,  as  representing  a  transition  from  sexual  to  asexual  reproduc- 
tion. Here  germ-cells,  which  often  appear  to  be  formed  exactly  like 
ova,  develop  into  new  individuals,  without  the  influence  of  any  fructify- 
ing sperm.  It  occurs  in  certain  plants  and  animals,  and  is  probably 
of  the  nature  of  a  relapse  from  the  sexual  method. 

Among  our  common  honey-bees,  male  individuals  arise  only  from 
unfertilized  eggs  by  parthenogenesis  ;  while  the  fertilized  eggs  originate 
females  exclusively,  which  evolve  into  fertile  forms  (queens),  or  sterile 
forms  (workers),  according  to  the  nature  of  their  food.  Moreover,  it 
appears  probable,  that  the  very  same  egg  may  develop  agamically  ; 
which,  under  other  circumstances,  would  have  been  fertilized.  These 
considerations  show,  that  there  is  no  such  fundamental  distinction 
between  gamogenesis  and  agamogenesis,  as  is  commonly  supposed. 

In  true  parthenogenesis  there  occurs  along  with  gamogenesis,  in  a 
true  ovarium  or  homologous  organ,  a  form  of  agamogenesis  exactly  like 
gamogenesis,  save  in  the  absence  of  fertilization,  as  in  silkworm  moths. 
False  parthenogenesis  occurs  when  new  individuals  arise  from  buds  in 
pseud- ovaria,  which  are  not  ova  properly  so  called,  as  in  Aphides. 

This  process  is  intermediate  between  true  parthenogenesis  and  that 
form  of  agamogenesis  called  by  Owen  metagenesis,  in  which  new  indi- 
viduals bud  out,  not  from  any  specialized  organs  ;  but  from  unspecialized 
parts  of  the  parent,  which  are  generally  external,  but  may  be  internal, 
as  in  distoma. 

Herein  we  have  evidence  that  the  reproductive  properties  of  somatic 
and  of  germ  cells  are  the  same  in  kind  ;  and  that  they  differ  only  in 
degree. 

We  now  pass  to  the  very  remarkable  series  of  events  known  as  the 
alternation  of  generations.  Until  comparatively  recently,  it  was  believed 
that  in  every  species  the  successive  generations  were  always  alike — 


208  THE  NATURAL  HISTORY  OF  CANCER 

homogenesis  ;  but  it  is  now  known  that  this  is  not  always  the  case — 
heterogenesis. 

Many  plants  and  animals  produce  a  generation  unlike  their  parents  ; 
these  may  produce  others  like  themselves,  or  like  their  parents,  or  like 
neither,  and  so  on  ;  but  eventually  the  original  form  reappears.  Here 
gamogenesis  alternates  with  agamogenesis  or  parthenogenesis. 

In  further  illustration  of  this  subject,  reference  may  be  made  to  the 
life-history  of  the  plant  lice  (Aphides),  which  has  been  admirably  worked 
out  by  Owen,  Huxley  and  others. 

The  impregnated  ova  of  the  Aphis  are  deposited  at  the  close  of  summer 
in  the  axils  of  the  leaves  of  the  plant  infested ;  retaining  their  vitality 
throughout  the  winter,  these  ova  are  hatched  by  the  returning  warmth 
of  the  spring  :  a  wingless  hexapod  larva  is  the  result.  In  the  pseud-ovaria 
of  these  imperfect  females,  there  bud  forth  pseud-ova,  which  rapidly 
develop  into  similar  imperfect  females.  At  this  season  no  winged  males 
have  appeared.  This  process  of  agamic  multiplication  continues  through- 
out the  summer.  If  the  external  conditions,  such  as  warmth  and  nutri- 
ment, continue  favourable,  eight  or  more  successive  generations  may  be 
thus  produced.  But,  when  the  weather  becomes  cold  and  the  supply 
of  sap  fails  in  the  plant,  perfect  males  and  females  are  produced,  which 
by  gamogenesis  reproduce  fertilized  ova,  thus  completing  the  cycle. 

Further  experiments  have  shown  that,  in  such  cases,  the  rapidity  of 
the  agamogenesis  is  proportionate  to  the  degree  of  warmth  and  nutri- 
tion ;  and  that,  if  the  temperature  and  food-supply  be  artificially  main- 
tained, the  agamogenesis  continues  throughout  the  winter.  When  the 
favourable  conditions  have  been  kept  up  for  several  successive  years, 
agamogenesis  has  likewise  continued.  In  short,  it  seems  probable  that 
this  agamic  reproduction  may  be  continued  indefinitely,  if  all  the  requisite 
conditions  be  fulfilled. 

Thus,  in  these  creatures,  the  summer  brood,  living  under  favourable 
conditions  of  nutrition,  reproduce  agamically  imperfect  females  ;  whereas, 
in  the  autumn,  under  less  favourable  conditions  of  nutrition,  perfect  males 
and  females  are  produced.  That  this  is  due  to  the  external  conditions, 
and  not  to  fixed  cyclical  routine  in  the  life-history  of  the  organism,  may 
be  inferred  from  the  fact,  that  in  the  favourable  environment  of  a  green- 
house, the  agamic  production  of  imperfect  females  may  continue  for 
years. 

This  connexion  between  sexual  reproduction  and  such  diminished 
nutrition  as  makes  growth  relatively  slow,  was  first  fully  made  known 
by  the  celebrated  biologist  Caspar  Friedrich  Wolff,  chiefly  from  the 
study  of  the  process  in  plants.  Viewed  in  this  light,  gamogenesis  is  seen 
to  be  nothing  but  a  particular  case  of  cell  multiplication  ;  and  impreg- 
nation merely  one  of  the  many  conditions  which  affect  the  process. 

Seeing  that  the  action  of  the  sperm-cell  on  the  germ-cell  was  the 
cause  of  its  development — for  before  it  was  deficient  in  this  respect — 
and  bearing  in  mind  such  considerations  as  the  above,  Wolff  was  led  to 
regard  the  former  as  nutriment  in  its  highest  perfection,  supplied  to  the 
germ-cell  from  without,  instead  of  through  the  ordinary  channels. 

If  we  ask  modern  biologists  how  fertilization  causes  the  ovum  to 


CANCER  AND  TUMOUR  GROWTH 


209 


grow  and  proliferate,  they  reply  that  it  is  due  to  the  action  of  local 
bio-chemical  or  zymotic  changes,  incited  by  some  substance  appertaining 
to  the  spermatozoon,  which  probably  concentres  in  its  centrosome  or 
nucleus,  and  is  therefore  exceedingly  minute  as  to  its  quantity.  According 
to  Boveri,  the  ripe  ovum  comprises  all  the  structures  and  qualities  neces- 
sary for  growth,  except  the  centrosome,  which  is  supplied  by  the  sperma- 
tozoon originating  the  process ;  Loeb,  however,  considers  that  the 
spermatozoon  acts  as  a  catalyzer,  merely  accelerating  a  process  which 
starts  of  its  own  accord. 

The  result  of  some  very  remarkable  experiments  in  the  artificial  pro- 
duction of  ovular  exegesis,  especially  point  to  the  importance  of  chemical 
stimuli. 

Under  normal  conditions,  the  growth  of  the  egg  of  the  annelid 
Chcetopterus,  pauses  at  the  first  polar  mitosis  until  fertilized  by  the  sper- 
matozoon, when  mitosis  is  resumed,  and  both  polar  bodies  are  formed. 


MC,  Cell  wall ;  pc,  cell  protoplasm,  showing  radiating  reticulum,  enclosing  fluid  plasma  ; 
mn,  wall  of  nucleus ;  pn,  nuclear  substance,  showing  reticulum  and]  plasma  ; 
bn,  contorted  bend  of  nuclein  or  chromatin. 

Mead  has  shown  that  the  same  effect  may  be  produced,  without 
fertilization,  by  placing  the  eggs  for  a  few  minutes  in  a  weak  solution  of 
chloride  of  potassium. 

Hertwig  demonstrated  that  the  unfertilized  eggs  of  sea-urchins  may 
be  incited  to  mitotic  multiplication,  by  treating  them  with  weak  solutions 
of  sulphate  of  strychnine. 

Morgan  found  that  the  unfertilized  eggs  of  sea-urchins  and  other 
echinoderms,  placed  for  an  hour  or  two  in  sea-water,  to  which  2  per 
cent,  of  the  chlorides  of  sodium,  potassium,  or  magnesium  had  been 
added,  would — when  replaced  in  normal  sea-water — enter  on  active 
segmentation,  the  entire  mitotic  system  being  evolved  under  the  incitation 
of  the  chemical  stimulus.  Morgan  also  repeated  and  confirmed  Hertwig's 
experiments,  as  to  the  similar  effects  caused  by  sulphate  of  strychnine. 

14 


210 


THE  NATURAL  HISTORY  OF  CANCER 


The  climax  of  these  experiments  was  reached  when  Loeb,  by  carefully 
regulating  the  strength  of  his  solutions  of  the  above-mentioned  chlorides 
and  other  reagents,  achieved  the  full  development  of  the  embryo  from 
the  unfertilized  sea-urchin's  egg.  Loeb  also  found  that  short  immersion 
of  the  unfertilized  sea-urchin's  egg  in  sea- water,  to  which  a  small  quantity 
of  acid  or  alkali  had  been  added,  would  start  segmentation.  It  was 
subsequently  shown  by  Matthews  and  others,  that  similar  changes  could 
be  incited  by  deprivation  of  oxygen,  by  heat,  mechanical  agitation,  ether, 
alcohol,  chloroform  etc.  ;  in  short,  it  seems  as  if  any  means  capable  of 


- 


FIG.  11. — DIAGRAM  OF  NUCLEAR  DIVISION  (WEISMANN). 

r*1  A,  Cell  with  nucleus  (n),  and  centrosomes  (cs),  preparatory  to  division.  The  chromatin 
forms  a  thickened  spiral  thread  (chr).  B,  The  nuclear  membrane  has  disappeared. 
Delicate  threads  radiate  from  the  centrosomes  and  form  a  nuclear  spindle,  at  the  equator 
of  which  eight  chromosomes  or  nuclear  loops  (Jd)  are  arranged,  formed  by  the  splitting 
up  of  the  spiral  thread  of  chromatin  in  A.  C,  The  chromosomes  have  each  become 
longitudinally  split  into  two,  and  are  about  to  be  drawn  apart  by  the  spindle  threads,  the 
daughter  loops  passing  towards  the  poles  of  the  spindle,  as  in  D.  The  cell  body  then 
divides,  each  of  the  resultant  cells  containing  a  centrosome  and  eight  nuclear  loops. 

producing  localized  liquefaction  of  the  egg  protoplasm,  may  suffice  to 
originate  mitotic  proliferation. 

Since  the  nucleus  is  so  largely  concerned  in  the  formative  changes 
which  cells  undergo,  it  is  here  necessary  to  refer  briefly  to  its  leading 
structural  features.  Under  ordinary  circumstances,  the  nucleus  usually 
presents  as  a  more  or  less  globular  vesicle  embedded  in  the  cytoplasm.  It 
comprises  a  very  fine  protoplasmic  reticulum,  the  meshes  of  which  are 
filled  with  granular  fluid  (plasma).  In  addition  to  these  achromatic 
substances,  the  nucleus  also  comprises  a  distinctive  proteid  phosphorus- 
containing  substance  called  nuclein,  or  from  its  staining  readily  chro- 
matin. In  young  cells,  this  substance  often  presents  as  a  long  irregularly 


CANCER  AND  TUMOUR  GROWTH  211 

contorted  filament  (Fig.  10)  ;  but,  in  mature  cells,  it  is  usually  condensed 
into  one  or  more  spherical  or  irregularly  shaped  masses,  which  constitute 
the  nucleoli.  It  is  in  this  chromatin  constituent  of  the  nucleus,  that  the 
formative  properties  of  the  cell  seem  specially  to  concentre  ;  and,  as  it  is 
the  only  nuclear  substance  which  passes  directly  from  cell  to  cell  during 
proliferation,  it  is  believed  to  be  the  material  bearer  of  hereditary  ten- 
dencies. In  cells  about  to  undergo  division,  besides  other  changes,  the 
nuclear  chromatin  experiences  a  remarkable  series  of  transformations, 
assuming  successively  the  forms  of  a  coil,  wreath,  star  etc.,  the  outcome 
of  which  is  that  the  chromatic  formation  is  eventually  resolved  into  a 
definite  number  of  rod-shaped  chromatin  bodies,  known  as  chromosomes, 
which  split  lengthwise  as  the  cell  divides — half  of  each  going  to  the 
nucleus  of  the  daughter  cells.  The  chromosomes  themselves  are  aggre- 
gates of  minute  chromatin  granules  (chromomeres). 

Every  species  of  animal  has  a  fixed  number  of  chromosomes,  which 
characterizes  the  division  of  all  its  cells  ;  for  mankind  the  number  has  not 
yet  been  certainly  determined,  but  it  is  generally  believed  to  be  sixteen, 
although  some  cytologists  put  it  as  high  as  thirty-two,  one-half  of  the 
number  being  derived  from  each  parent.  The  essence  of  this  process  of 
division  is,  that  the  chromatic  thread,  whether  continuous  or  discon- 
tinuous, splits  throughout  its  entire  length  into  two  exactly  similar 
halves ;  which  are  then  transported  in  opposite  directions,  to  the  respective 
poles  of  the  achromatic  spindle,  whence  they  enter  into  the  formation  of 
the  two  corresponding  daughter  nuclei,  each  of  which  thus  receives  its 
half  share  of  the  chromatin,  the  movement  being  effected  and  the  spindle 
formed  under  the  influence  of  the  centrosomes. 

All  somatic  cells  multiplying  by  mitosis  are  thought  to  divide  in  this 
manner,  the  nuclei  of  the  daughter  cells  having  exactly  as  many  chromo- 
somes, as  the  parent  cell. 

In  1883,  Van  Beneden  discovered  that  the  nuclei  of  conjugating  germ- 
cells,  contained  only  one-half  of  the  number  of  chromosomes  charac- 
teristic of  the  somatic  cells  ;  and  subsequently  it  was  proved  that  this 
"  reduction  of  the  chromosomes  "  was  a  universal  feature  in  the  matura- 
tion of  gamogenetic  germ-cells.  The  peculiar  feature  of  the  process  is, 
that  the  chromatin  is  rearranged  and  redistributed,  without  the  loss  of 
any  of  its  essential  constituents.  It  is  clear  that  this  reduction  is  a  pre- 
paration of  the  germ-cells  for  their  subsequent  union  ;  and  the  means  by 
which  the  number  of  chromosomes  is  kept  constant  for  the  species.  In 
fact,  the  essence  of  fertilization  consists  in  the  placing  in  juxtaposition 
of  an  equal  number  of  the  chromosomes  of  each  parent ;  so  that  the 
offspring  may  contain  all  the  essential  constituents  of  the  chromosomes  of 
both  parents  in  about  equal  measure.  Weismann  believes  that  this  reduc- 
tion is  effected  by  the  extrusion  of  the  second  polar  body,  which  removes 
with  it  the  one-half  of  the  chromosomes  not  needed  for  gamogenesis. 

Recent  researches  seem,  however,  to  indicate  that  similar  reduction 
may  also  occur  in  the  chromosomes  of  somatic  cells,  under  certain  con- 
ditions at  present  but  little  understood  ;  hence,  it  is  evident  that  the 
problem  of  reduction  and  its  significance,  is  still  far  from  having  been 
adequately  solved. 

14—2 


212  THE  NATURAL  HISTORY  OF  CANCER 


Tumour  Growth. 

All  that  we  know  of  tumours  indicates,  that  they  grow  and  are 
nourished  like  normal  parts  of  the  body  ;  hence,  the  growth  of  tumours, 
like  normal  growth,  is  influenced  and  determined — directly  or  indirectly — 
chiefly  by  the  conditions  of  nutrition,  as  above  set  forth. 

We  have  already  seen  that  the  germs  of  histioid  tumours  are  cells  of 
somatic  origin  ;  and  that  the  essence  of  the  neoplastic  process  consists 
in  the  awakening,  in  these  cells,  of  more  intense  power  of  growth  and 
proliferation  than  is  normal. 

Viewed  in  this  light,  tumour  formation  may  be  regarded  as  a  dis- 
turbance of  the  rhythm  of  growth,  by  the  interpolation  in  the  develop- 
mental series  of  redundant  agamic  cell  generations,  owing  to  altered 
conditions  of  nutrition. 

Thus  the  growth  of  cancers — like  discontinuous  growth  in  general, 
of  which  it  is  but  a  particular  case — is  the  outcome  of  a  disintegrative 
process,  being  distinctly  related  to  the  decline  of  growth — "  senescence  " 
— of  the  body  in  general,  and  especially  of  the  particular  local  tissues. 
Hence,  while  the  forces  of  growth,  development,  and  reproduction  are  in 
greatest  activity — during  the  periods  of  pre-natal  life,  infancy,  child- 
hood, adolescence,  and  even  adult  age — the  tendency  to  this  disease 
is  comparatively  small.  In  both  sexes,  it  begins  to  be  of  great  frequency 
in  the  post-meridian  period. 

Thus  the  tendency  to  cancer-growth  waxes,  as  the  developmental  and 
reproductive  activities  wane.  The  antagonism  between  the  forces  of 
genesis,  growth,  development,  and  expenditure,  is  the  same  in  pathology 
as  in  physiology.  In  this  we  see  illustrated  the  universal  biological  law  : 
that  growth  varies  according  to  the  surplus  of  nutrition  over  expenditure. 
So  long  as  the  surplus  exists,  that  is  to  say,  while  growth  is  active  and 
nutrition  relatively  high,  simple  continuous  increase  is  maintained  ; 
but,  when  growth  declines  and  nutrition  is  relatively  low,  that  is  to  say. 
when  it  is  nearly  equalled  by  expenditure,  new  centres  of  development 
are  apt  to  arise,  and  growth  tends  to  become  discontinuous.  Changes  of 
nutrition  determine  the  transition  from  the  one  to  the  other  mode  of 
increase  ;  and  so  favour  the  growth  of  cancer  and  other  tumours,  as  I 
have  previously  indicated. 

The  physiological  paradigms  of  the  neoplastic  process  are  to  be  found 
in  gemmation  or  agamogenesis — especially  in  that  form  of  it  called 
metagenesis,  in  which  the  new  formations  bud  out,  not  from  special 
organs,  but  from  somatic  elements  of  the  parent,  whether  these  are  situ- 
ated externally  or  internally — and  even  in  parthenogenesis.  In  excelsis 
all  of  these  forms  of  growth  tend  to  be  discontinuous,  and  they  are 
essentially  of  reproductive  import ;  but  it  does  not  necessarily  follow  that 
such  is  always  their  destiny — the  process  may  have  a  more  or  less  abortive 
ending,  eventuating  for  instance  in  tumour  formation. 

When  agamic  processes  of  this  kind  end  in  the  formation  of  new 
individuals,  it  may  be  assumed  that  this  is  a  result  of  their  germinal  cells 
having  acquired  complete  emancipation  from  the  integrative  control  of 


CANCER  AND  TUMOUR  GROWTH  213 

the  parental  organism  ;  and,  conversely,  when  only  such  abortive  pro- 
ducts as  tumours  are  evolved,  the  emancipation  of  the  germinal  cells 
from  this  control  may  be  assumed  to  be  much  less  complete. 

The  fundamental  nature  of  the  setiological  connexion  between  these 
processes  and  the  conditions  of  nutrition,  I  have  already  sufficiently 
indicated. 

In  mankind  and  the  higher  animals,  except  in  the  very  earliest  stages 
of  ontogenetical  development — as  we  have  already  seen — no  cells  (except 
the  ova,  which  are  so  differentiated  that  they  cannot  respond,  until  they 
have  undergone  maturation  and  fertilization)  are  ever  completely  eman- 
cipated ;  hence  in  these,  instead  of  new  individuals,  such  abortive 
formations  as  tumours  result. 

From  this  standpoint,  tumour  formation  may  be  regarded  as  a  lapse 
from  predominant  gamogenesis,  in  the  direction  of  agamogenesis  ;  for,  as 
the  individuality  of  tumours  especially  indicates,  the  process  is  essentially 
of  a  reproductive  or  disintegrative  nature. 

In  like  manner,  the  different  qualities  manifested  by  malignant  and 
non-malignant  tumours  may  be  interpreted,  as  I  have  explained  in 
Chapter  VII. 

I  have  previously  had  occasion  to  refer  to  the  misleading  efforts  of 
some  biologists,  to  indoctrinate  belief  in  a  fundamental  specific  distinc- 
tion between  somatic  and  germ  cells,  which  the  most  detailed  histological 
analysis  of  cellular  structure  fails  to  support ;  and  which  is  contravened 
in  the  plainest  manner,  by  many  of  the  most  fundamental  and  important 
facts  in  the  whole  range  of  biology,  as  I  have  elsewhere  indicated. 

With  regard  to  this  doctrine,  it  may  truly  be  said,  that  it  has  no  real 
foundation  in  fact  :  it  is,  indeed,  the  outcome  of  "  muddy  speculation," 
starting  from  an  essentially  faulty  conception  ;  and,  as  such,  it  must  be 
regarded  as  being  entirely  outside  the  pale  of  scientific  truth. 

As  E.  B.  Wilson,  the  chief  exponent  of  modern  cytological  knowledge 
for  English-speaking  people,  has  so  well  said,  in  the  latest  edition  of  his 
useful  book  i1  "All  the  facts  at  our  command  indicate,  that  the  tissue 
cell  possesses  the  same  morphological  organization  as  the  egg-cell,  or  the 
protozoan  ;  and  the  same  fundamental  physiological  properties  as  well." 

There  can,  then,  be  no  doubt,  as  Spencer  and  Darwin  surmised,  that 
the  fundamental  properties  of  somatic  and  germ  cells  are  the  same  in 
kind,  and  that  they  differ  only  in  degree. 

In  the  growth  of  malignant  tumours,  as  in  the  growth  of  normal 
tissues,  differentiation  and  proliferation  seem  to  be  inversely  related. 
In  a  certain  general  way,  it  may  be  said  of  the  metabolism  of  malignant 
tumours,  that  the  habit  of  growth  predominates  over  the  habit  of  function 
(Adami).  In  some  animals,  it  has  been  found  that  differentiation  is 
concomitant  with  the  loss  of  certain  nuclear  structures  ;  and  Boveri  has 
suggested,  that  the  exceptional  regenerative  power  of  some  organisms, 
may  be  due  to  retention  in  latent  state,  by  differentiated  somatic  cells, 
of  reproductive  properties  derived  from  the  fertilized  egg.  It  may  be 
inferred  from  these  considerations,  that  growing  tumour  germs  owe  their 
unusual  proliferative  capacity,  to  the  relative  non-involvement  of  their 
nuclear  substance  in  the  specific  changes  which  determine  differentiation. 
1  "  The  Cell  in  Development,"  etc.,  1904,  p.  291. 


214  THE  NATURAL  HISTORY  OF  CANCER 


Recapitulation  and  General  Conclusions. 

In  concluding  this  stage  of  the  argument,  a  brief  recapitulation  of  the 
chief  items  thereof  may  be  useful. 

Besides  such  general  causative  factors  of  growth  as  I  have  had  occasion 
to  mention,  which  are  chiefly  the  outcome  of  intrinsic  forces,  there  are 
also  other  considerations  which  affect  the  process.  Thus,  for  instance, 
with  the  growth  from  the  ovum,  although  the  stimulus  of  fertilization  is 
generally  necessary  for  its  accomplishment ;  yet,  the  process  starts 
independently,  and  is  merely  accelerated  and  completed  thereby.  That 
this  stimulus  is  not  always  necessary,  is  shown  by  the  life-history  of  the 
common  bee,  whose  unfertilized  ova  grow  "  spontaneously  "  into  males, 
while  the  very  same  ova,  when  fertilized,  grow  into  females  ;  of  like 
import  are  the  cases  of  "  true  "  parthenogenesis,  wherein  cells — which 
are  indistinguishable  from  ova— grow  into  new  beings,  without  any  such 
external  stimulus.  In  metagenesis,  and  in  other  forms  of  agamogenesis, 
we  see  unspecialized  somatic  cells  of  diverse  parts  of  the  body — which  are 
certainly  neither  germ-cells  nor  ova  in  the  usually  accepted  sense  of 
these  terms — nevertheless,  endowed  with  the  power  of  growing  into  new 
individuals,  without  any  other  stimuli  than  those  provided  by  the  rhythm 
of  growth  and  favourable  conditions  of  nutrition.  Then,  finally,  we  see 
growth  from  the  ovum  incited,  and  even  urged  to  its  completion,  by 
various  chemical  stimuli  and  other  extrinsic  factors.  Thus,  the  evidence 
that  the  reproductive  properties  of  somatic  and  germ  cells  are  the  same 
in  kind,  and  differ  only  in  degree,  is  full  and  complete. 

It  is  in  the  light  of  such  considerations,  that  the  problem  of  the 
growth  of  histioid  tumour  germs  must  be  studied.  Indeed,  it  seems 
certain  that  the  conditions,  both  general  and  special,  which  determine 
tumour  growth,  are  similar  to  those  concerned  in  the  regulation  of  these 
its  physiological  paradigms. 

Thus,  in  the  pathological  as  in  the  physiological  process,  besides  the 
general  causative  factors  of  growth,  various  other  conditions  seem  to 
affect  the  process. 

With  regard  to  the  influence  of  nutrition,  of  which  I  shall  have  more 
to  say  in  the  sequel,  I  will  now  only  remark  ;  that  tumours  grow,  because 
the  bodies  of  the  affected  persons  contain  an  abundance  of  materials 
suitable  for  their  nutrition,  and  stimulating  to  their  formative  meta- 
bolism. 

Thus,  cancerous  tumours  consist  almost  exclusively  of  albuminous  or 
proteid  substances  ;  and,  it  seems  not  unreasonable  to  suppose,  that  their 
growth  may  be  favoured  by  excess  of  these  substances  in  the  body — and 
especially  of  such  of  them  as  serve  as  nuclear  pabulum.  When  excessive 
quantities  of  such  highly  stimulating  forms  of  nutriment  are  ingested, 
by  persons  whose  metabolism  is  defective — whether  by  reason  of 
senescence  or  otherwise — there  may  thus  be  excited,  in  those  parts  of 
the  body  where  proliferative  processes  are  still  potentially  active,  such 
excessive  and  disorderly  cellular  proliferation  as  may  eventuate  in 
cancer.  However  this  may  be,  I  am  persuaded  that  the  ascertained 


CANCER  AND  TUMOUR  GROWTH  215 

facts  justify  the  belief,  that  there  is  a  certain  relation  between  the  con- 
ditions of  nutrition  and  the  incidence  of  cancer  growth. 

It  seems  to  me  quite  clear,  that  the  growth  of  malignant  tumours  is 
also  favoured  by  the  altered  metabolism  of  the  body,  consequent  on 
decline  of  the  reproductive  function.  The  age-incidence  of  the  disease 
accords  with  this ;  and  of  similar  import  is  the  fact,  that  malignant 
growths  in  women  occur  with  great  and  altogether  disproportionate  fre- 
quency, after  removal  of  the  ovaries  for  various  non-malignant  affections  ; 
after  the  destruction  of  their  essential  elements  in  the  course  of  disease  ; 
and  in  cases  of  congenital  absence  or  defect  thereof,  of  which  I  shall  have 
to  say  more  in  the  sequel.  The  great  frequency  of  malignant  growths 
in  castrated  cattle  of  both  sexes,  to  which  Sticker  x  has  specially  called 
attention  points  to  the  same  conclusion  ;  thus,  of  200  bovine  animals  with 
malignant  tumours  tabulated  by  him,  no  less  than  100  were  castrates  ; 
and  of  120  horses  with  malignant  tumours,  51  were  castrates. 

It  has  been  suggested  that  other  organs,  besides  the  sexual  glands, 
may  also  influence  the  general  metabolism  in  such  a  way,  as  to  retard  or 
favour  the  growth  of  cancer.  Although,  in  this  connexion,  there  is 
absence  of  any  decisive  evidence,  such  as  is  forthcoming  in  favour  of  the 
r61e  of  the  sexual  glands  ;  it  seems  desirable,  in  accordance  with  the  plan 
of  this  work,  briefly  to  review  this  line  of  inquiry,  especially  as  it  may 
throw  some  light  on  the  obscure  processes  of  metabolism,  with  which 
tumour  growth  is  so  intimately  bound  up. 

The  growth  of  the  epithelial  tissues  of  the  body  certainly  varies  much, 
and  is  differently  conditioned,  at  different  periods  of  life.  In  infancy  and 
childhood,  as  compared  with  the  other  tissues,  the  epithelia  are  com- 
paratively inactive  ;  and,  it  seems  probable,  that  the  immunity  of  children 
from  malignant  epithelial  growths,  is  in  some  way  connected  with  this 
physiological  quiescence.2  By  what  means  then,  in  the  healthy  body,  is 
epithelial  growth  inhibited  and  kept  within  due  limits  ?  To  this  query, 
the  chemical  physiologist  answers  :  that  it  is  due  to  certain  bio-chemical 
reactions,  in  which  enzymes  play  a  leading  part — "  anti-epithelial  " 
substances  being  thus  formed,  which  circulating  throughout  the  body 
check  the  growth  of  epithelial  cells.  In  like  manner,  the  chemical 
pathologist  refers  the  exuberant  epithelial  growth  of  cancer,  to  absence 
or  deficiency  of  these  special  substances. 

The  organs  more  particularly  concerned  in  influencing  these  hypo- 
thetical processes  are,  according  to  Sajous,  the  adrenals,  the  thymus, 
the  thyroid,  and  the  anterior  part  of  the  pituitary  body — the  adrenal 
influence  predominating.  Thus  Sajous3  says:  "Certain  growths,  par- 
ticularly the  more  malignant  forms  of  sarcoma  and  carcinoma,  seem 
closely  connected  with  adrenal  insufficiency  and  its  normal  consequences. 
We  have  seen  that  trypsin,  fibrinogen  and  the  oxidizing  substance,  were 
simultaneously  necessary  to  ensure  the  destruction  of  cells  in  vitro  ; 
and,  furthermore,  that  this  process  required,  in  addition,  the  presence  of 
alkaline  salts.  That  the  destruction  of  worn-out  or  degenerated  cells, 
is  a  function  of  these  very  elements  in  the  blood,  is  evident.  Insufficiency 

1   Arch.  f.  klin.  Chir.,  1902,  Bd.  Ixv.,  Heft  3  and  4.  2  Vide  Chapter  XV.  jj 

3  "  Internal  Secretions,"  1903,- vol.  i.,  p.  785,  Philadelphia,  U.S. 


216  THE  NATURAL  HISTORY  OF  CANCER 

of  the  adrenals  therefore,  by  reducing  the  relative  proportions  of  these 
four  constituents  in  the  blood-stream,  must  correspondingly  inhibit  this 
physiological  process  in  all  parts  of  the  system." 

In  comparatively  recent  times  some  remarkable  instances  have  been 
reported,  which  show  that  there  is  some  setiological  connexion  between 
ovarian  and  adrenal  integrity  ;  and  the  growth  of  malignant  tumours. 
Thus,  as  I  have  specially  pointed  out,  in  a  publication  on  "  Precocious 
Sexual  Development,"  -1  this  anomaly  is  fairly  often  associated  with 
malignant  ovarian  and  adrenal  tumours.  Bullock,  Sequeira,  Linser, 
Adams  2  and  Guthrie  3  have  lately  reported  additional  examples  of  this 
kind,  associated  with  malignant  adrenal  tumours  ;  and  I  have4  elsewhere 
cited  instances  of  malignant  tumours  of  various  parts  of  the  body,  con- 
comitant with  non-malignant  adrenal  tumours. 

Here  also  it  may  be  mentioned  that  Drs.  Beard  and  Shaw-Mackenzie,5 
have  ascribed  cancer  growth  to  perverted  metabolism  caused  by  hypo- 
thetical failure  of  pancreatic  secretion,6  especially  of  trypsin  ;  and  they 
claim  to  have  cured  "  Jensen's  tumour  "  in  mice — which  so  often  under- 
goes spontaneous  cure — with  injections  of  this  substance. 

Whatever  element  of  truth  may  be  concealed  in  these  obscure  pro- 
cesses, it  appears  to  me  that  these  therapeutic  suggestions  go  far  beyond 
what  is  warranted  by  the  known  facts  ;  indeed,  it  is  only  with  regard  to 
thyroid  medication — which  seems  to  exert  beneficial  influence  on  some 
hyperplastic  cutaneous  maladies,  and  even  on  certain  cancerous  growths — 
that  we  can  be  said  to  have  any  facts  at  all  worthy  the  name,  and  these 
are  far  from  warranting  such  sensational  inferences  as  have  been  drawn. 

If  then  I  have  referred  to  these  matters  at  all,  it  is  because  of 
the  possible  prospective  value  of  this  kind  of  research,  rather  than  for 
anything  that  has  as  yet  been  ascertained. 

We  have  already  seen  that  the  tissue  cells  may  be  incited  to  abnormal 
growth  and  proliferation  by  some  traumata,  by  the  toxins  of  certain 
microbes,  by  various  chemical,  electrical,  thermal,  mechanical,  and  other 
extrinsic  agencies  ;  although  none  of  these  seem  able,  per  se,  to  carry  the 
process  on  to  true  tumour  formation.  Thus  tumour  germs  resemble  ova, 
in  that  they  generally  require  to  be  matured  and  stimulated  in  a  par- 
ticular way,  before  their  potential  proliferative  power  can  become  actual. 

From  this  standpoint,  the  problem  of  cancer  growth  resolves  itself 
into  a  research,  to  determine  the  particular  way  in  which  the  cells  of 
tumour  germs  may  be  incited  to  unfold — in  sufficient  measure — their 
potential  proliferative  capacity. 

Although  it  is  probable  that  in  the  past,  the  value  of  extrinsic  factors, 
as  formative  stimuli,  have  been  underrated ;  it,  nevertheless,  seems 
probable,  from  the  whole  course  of  ontological  growth,  that,  in  tumour 
formation,  as  in  normal  growth,  intrinsic  factors  usually  predominate. 

1  British  Gynaecological  Journal,  May,  1902. 

2  Transactions  of  the  Pathological  Society,  London,  1905,  vol.  Ivi.,  p.  189. 

3  British  Medical  Journal,  September  21,  1907. 

4  Chapter  XIII. 

5  Medical  Press  and   Circular,   December  20,    1905,   p.    661  ;    see    also    Dr.    Shaw- 
Mackenzie's  "  Nature  and  Treatment  of  Cancer,"  1905. 

5  As  will  be  mentioned  later  on,  cancer  of  the  pancreas  is  comparatively  rarely 
associated  with  glycosuria. 


CANCER  AND  TUMOUR  GROWTH  217 

If  we  ask  cytologists  to  explain,  How  it  is  that  ova  sometimes  develop 
parthenogenetically  ?  they  reply,  that  it  is  due  to  imperfect  matura- 
tion ;  for,  cells  undergoing  this  kind  of  growth,  extrude  only  a  single  polar 
body,  and  consequently  undergo  no  reduction  of  the  nuclear  chromo- 
somes, which  is  effected  by  the  extrusion  of  the  second  polar  body,  and  is 
preparation  for  fertilization.  Pursuing  the  analysis  further,  they  main- 
tain that,  in  parthenogenesis,  the  second  polar  body  is  not  really  absent, 
but  only  abortive  ;  and  that  this  kind  of  growth  is  the  result  of  the  self- 
fertilization  of  the  ovum,  by  its  abortive  second  polar  body. 

There  are,  however,  good  reasons  for  believing,  that  this  interpreta- 
tion of  the  process  is  far  from  being  adequate,  since  the  ova  of  certain 
arthropods  have  been  seen  to  develop  parthenogenetically,  although 
— like  ova  which  require  fertilization — they  have  produced  two  polar 
bodies,  and  have  undergone  reduction  of  the  chromosomes.  Never- 
theless, pathological  cytologists  are  now  asking,  whether  conditions 
of  this  kind  may  not  play  a  part  in  the  growth  of  tumour  germs  ?  So 
far  as  I  know,  no  one  has  ever  observed  in  the  germ-cells  of  cancer, 
maturation  phenomena  like  those  seen  in  normal  or  parthenogenetical 
ova ;  that  is  to  say,  the  formation  of  polar  cells — unless,  indeed,  some 
observations  by  Paterson *  may  be  interpreted  in  this  sense.  It  has, 
however,  long  been  known,  as  specially  indicated  by  Hansemann,2  that 
among  the  numerous  mitotic  irregularities  of  growing  cancer  cells,  a 
deficiency  of  the  chromosomes  ("  hypochromatic  ")  is  often  noticeable  ; 
lately,  Farmer.  Moore  and  Walker,3  have  described  the  occurrence  of 
reduction  of  the  chromosomes  ("  hetero typical  mitosis ") — like  that 
normally  met  with  in  maturing  germ-cells — as  being  a  constant  and 
special  feature  of  the  growth  of  malignant  tumours. 

Considering  how  little  is  known  as  to  the  occurrence  of  this  reducing 
process  in  human  tissues,  cytologists  not  even  being  in  agreement  as  to 
the  precise  number  of  chromosomes  proper  to  ordinary  somatic  mitosis, 
this  generalization  seems  rather  premature  ;  and,  it  accords  with  this, 
that  reduction  of  the  chromosomes  in  somatic  mitosis  has  already  been 
reported  in  various  processes,  having  nothing  to  do  with  cancer  ;  and  it 
has  even  been  found  possible  to  produce  it  artificially  by  chemical  stimula- 
tion etc.,  as  previously  mentioned. 

It  is  generally  stated  that  among  tumours,  only  the  malignant  ones 
exhibit  this  form  of  nuclear  arrangement ;  but  Bonney  4  has  met  with  it 
in  condylomata,  and  in  ovarian  papillomata. 

Since  then  reduction  of  the  chromosomes  is  not  constant  in  malignant 
tumours,  and  since  it  occurs  in  the  absence  of  malignancy,  whatever  its 
significance  may  be,  it  cannot  be  regarded  as  specific  of  cancer.  It  is 
even  just  possible,  that  reduction  may  eventually  turn  out  to  be  merely 
a  phase  of  senescence  in  certain  tissues. 

It  was  long  ago  remarked  by  pathological  cytologists,5  that  the 

1  Practitioner,  May,  1904. 

2  Arch.  f.  path.  Anat.,  1890,  Bd.  cxix.,  S.  299  ;  also  1891,  Bd.  cxxiii.,  Heft  2. 
"  Cytological  Investigation  of  Cancer,"  Liverpool,  1906. 

4  Transactions  of  the  Pathological  Society,  London,  1905. 

5  Transactions    of    the    Pathological    Society,    London,    1888,    vol.    xlix.,    p.    409 
(Shattock  and  Ballance). 


218  THE  NATURAL  HISTORY  OF  CANCER 

nuclei  of  growing  cancer  cells  have  a  tendency  to  shed  their  chromatin 
into  the  cytoplasm,  as  a  sort  of  preliminary  to  division  ;  and  to  this 
source  the  detached  nuclear  fragments,  described  by  Foa1  as  corps 
colorables,  were  generally  ascribed.  Paterson  2  has  lately  reinvestigated 
this  subject,  and  found  that  during  mitosis  certain  of  the  nuclei  throw 
out  processes  like  pseudo-podia,  this  being  the  first  stage  of  budding, 
or  the  beginning  of  the  migration  of  the  nuclear  chromatin  from  the  cell. 
The  appearances  seemed  to  indicate,  that  such  extruded  chromosomes, 
and  the  remainders  of  such  reduced  nuclei,  may  unite  by  mitosis  with 
similarly  affected  nuclei  from  other  adjacent  cells,  introducing  conditions 
having  some  resemblance  to  those  described  in  the  formation  of  abortive 
polar  bodies,  and  in  the  maturation  of  parthenogenetic  eggs.  Whether 
this  interpretation  of  the  mechanics  of  cancer  growth  will  eventually 
be  substantiated,  remains  to  be  seen. 

Pathologists  have,  of  course,  long  been  familiar  with  the  conception 
which  ascribes  the  initiation  of  malignant  growth,  to  the  conjugation  of 
the  cell  of  a  cancer  germ,  with  some  adjacent  somatic  cell,  as  described 
by  Strcebe,3  Hansemann,  Klebs  and  others  ;  but  it  cannot  be  said  that 
the  doctrine  thus  advanced  carried  much  conviction.  Lately,  as  the 
outcome  of  such  research  tendency  as  we  are  now  pursuing,  this  matter 
has  again  cropped  up. 

That  leucocytes  may  not  unfrequently  be  found  between,  and  even 
within,  the  constituent  cells  of  cancerous  tumours,  has  long  been  well 
known.  Lately,  Farmer,  Moore  and  Walker,4  examining  quite  young 
cancer  formations,  found  that  the  histological  appearances  indicated  a 
kind  of  conjugation  between  the  local  epithelial  cells  and  included 
leucocytes,  with  mixing  of  the  chromosomes  of  the  respective  nuclei 
during  mitosis,  but  apparently  without  reduction  ;  and  to  this  they  ascribe 
cancer  growth. 

In  studying  the  cytology  of  cancer  pathologists,  as  a  rule,  have  paid 
but  little  attention  to  the  centrosome,  to  which  biologists  attach  such 
great  importance,  as  the  directing  centre  of  formative  changes. 

In  1893,  however,  Galeotti  andLustig5  clearly  identified  the  centro- 
somes  in  cancer  cells  ;  and  published  descriptions  and  drawings  of  them. 
In  resting  cells,  they  found  a  single  centrosome  in  a  depression  at  the 
margin  of  the  nucleus  ;  but,  in  cells  entering  on  mitosis,  the  two  centro- 
somes  were  found  one  at  each  apex  of  the  mitotic  spindle. 

Borrel 6  next  identified  certain  rounded  "  endocytes  "  or  "  inclusions  " 
commonly  found  in  cancer  cells,  and  often  described  as  sporozoa  or 
coccidia,  as  being  the  cell  archoplasm  with  its  contained  centrosomes, 
with  which  he  had  previously  gained  familiarity  when  studying  the 
spermatogenesis  of  guinea-pigs. 

Le  Count,7  as  the  outcome  of  a  similar  study,  supported  these  con- 

Gaz.  degli  Ospitali,  February  2,  1893. 

Op.  cit. 

Ziegler's  Beitrage  z.  path.  Anat.,  1891,  Bd.  xi.,  S.  1. 

British  Medical  Journal,  1905,  vol.  ii.,  p.  314  ;  and  op.  cit. 

Ziegler's  Beitrage  z.  path.  Anat.,  1893,  Bd.  xiv.,  S.  225. 
f6  Ann.  de  I'Inst.  Pasteur,  1901,  vol.  xv.,  No.  2. 
7  Journal  of  Medical  Research,  vol.  vii.,  p.  383. 


CANCER  AND  TUMOUR  GROWTH  219 

elusions  ;  while  Hansemann  also  included  the  archoplasm,  as  one  among 
the  many  conditions  which  give  rise  to  "  endocytes  "  in  cancer  cells. 

Benda,1  having  found  intact  centrosomes  in  cancer  cells,  in  which 
"  endocytes "  were  also  present,  claims  that  this  disproves  Borrel's 
interpretation  as  to  their  analogy. 

Farmer,  Moore  and  Walker,2  having  lately  retraversed  the  same 
ground,  conclude  that  these  "  endocytes  "  represent  not  the  centro- 
somes, which  were  discernible  elsewhere  in  the  cells  ;  but  the  cast-off 
archoplasmic  vesicle,  in  which  the  centrosomes  were  originally  con- 
tained. 

Whatever  the  real  nature  of  these  "  inclusions  "  may  be,  they  are 
evidently  not  peculiar  to  cancer,  as  Greenough  3  and  so  many  others  have 
shown. 

Indeed,  it  is  as  yet  far  too  early  to  estimate  the  precise  significance 
attaching  to  the  various  recent  cytological  findings  in  cancer  cells  ;  but, 
already  it  can  be  clearly  discerned,  that  none  of  them  are  specific  of 
malignancy. 

The  most  searching  morphological  investigations,  having  failed  to 
reveal  any  specific  mark  of  malignancy,  pathologists  are  now  seeking 
for  some  chemical  materies  morbi. 

Like  so  many  of  our  modern  conceptions,  this  is  an  old  favourite  in 
new  dress.  Over  half  a  century  ago,  in  the  days  of  J.  Miiller  4  and  Lebert,5 
the  chemistry  of  tumours  was  very  thoroughly  studied,  with  the  same 
objective  in  view  ;  but  no  specific  substance  was  discovered.  The  general 
outcome  of  these  researches  was,  that  the  greater  the  malignancy  of  the 
tumour,  the  more  albuminous  substances  predominated  in  its  compo- 
sition ;  hence  Rokitansky6  proclaimed  that  diseased  ("  kakoplastic  ") 
albumin,  was  the  cause  of  all  true  malignant  tumours. 

Modern  physiologists  have  advanced  the  hypothesis,  that  the  develop- 
ment of  particular  structures  is  determined  by  specific  formative  sub- 
stances, which  incite  corresponding  kinds  of  metabolic  activity  and 
differentiation  :  the  nucleus,  they  regard  as  a  storehouse  of  ferments, 
which  pass  out  into  the  cytoplasm,  and  there  set  up  specific  activities. 

In  like  manner,  some  modern  pathologists  ascribe  the  initiation  of 
cancer  growth,  to  bio-chemical  disturbance  of  the  relations  normally 
subsisting  between  cell,  nucleus  and  protoplasm  ;  in  which,  as  the  result 
of  catalysis,  there  is  assumed  to  be  some  unusual  mingling  of  enzymes. 

According  to  Blumenthal 7  and  Hemmeter,8  cancer  cells  differ 
chemically  from  somatic  cells,  comprising  substances  that  have  hitherto 
not  been  found  in  the  normal  body  ;  while  Petry  claims  that  there  is  a 
special  intra-cellular  cancer  ferment — which  has  been  called  "  malignin  " 
— by  means  of  which  cancer  cells  are  endowed  with  their  special  qualities. 
These  conceptions  have  very  little  basis  in  ascertained  fact ;  they  are 

Verhandlungen  d.  deuts.  Gesellach.  f.  Chir.,  1902,  No.  31,  S.  73. 

Proceedings  of  the  Royal  Society,  1905. 

Third  Report  of  the  Croft  Cancer  Commission,  Boston,  U.S.,  1905. 

"  Ueber  den  feineren  Ban  und  die  Formen  der  krankhaften  Geschwiilste,"  1838. 

"Traite  d'Anat.  Path.,"  etc.,  Paris,  1857. 

"  Handb.  der  allgern.  path.  Anatomic,"  Wien,  1846,  S.  530. 

Berlin,  klin.  Woch.,  1905,  Nos.  12  to  15. 

American  Journal  of  Medical  Science,  April,  1903. 


220  THE  NATURAL  HISTORY  OF  CANCER 

rather  the  outcome  of  a  priori  considerations,  and  differ  but  little  from 
Rokitansky's  "  kakoplastic  "  albumin,  and  other  kindred  speculations, 
which  have  long  since  been  forgotten. 

Thus  chemistry,  like  morphology,  has  failed  to  reveal  any  specific 
cancer  substance,  from  whose  presence  this  malady  must  result. 

In  the  light  of  these  long-continued  and  repeated  failures,  we  shall 
probably  not  be  far  wrong  in  concluding  that  there  are  no  specific  cancer 
substances,  other  than  such  as  are  concerned  in  determining  the  specificity 
of  the  various  physiological  tissue  elements. 

It  will  be  gathered  from  the  foregoing,  that  far  more  may  be  learnt, 
as  to  the  real  nature  of  the  cancerous  process  and  the  conditions  which 
determine  it,  from  study  of  the  general  laws  of  growth  and  its  rhythm, 
and  of  their  relation  to  the  conditions  of  existence,  which  comprise 
nutrition  ;  than  from  the  mere  pursuit  of  details  —  morphological  and 
chemical — in  ultimate  analysis,  which  lead  to  nothing  more  stable  than 
a  chaos  of  hypothetical  "  enzymes,"  or  to  other  equally  unreliable  meta- 
physical notions — such  as  credulous  and  unscientific  epochs,  like  the 
present,  are  particularly  apt  to  engender. 


Growth,  Repair,  Regeneration,  and  Tumour  Growth. 

It  now  remains  for  me  to  offer  some  further  remarks  on  that  part 
of  this  important  subject,  which  relates  to  repair  and  the  regeneration  of 
lost  parts,  as  prototypes  of  tumour  formation. 

In  the  case  of  crystal  formation,  it  is  obvious  that  the  whole  aggregate 
exerts  a  force,  which  constrains  newly  integrated  units  to  take  a  certain 
form  ;  and  thus  crystals  are  enabled  to  repair  injuries. 

It  seems  probable  that  the  rearrangements  of  organic  units,  which 
characterize  the  processes  of  repair  aJid  regeneration  in  animals,  are 
determined  in  a  similar  way. 

According  to  Herbert  Spencer,  cells  capable  of  growth  completely 
uncontrolled  and  placed  in  fit  conditions,  naturally  tend  to  arrange 
themselves  into  the  form  of  the  organism  whence  they  originated  ;  thus, 
a  small  detached  bit  of  a  Hydra,  soon  moulds  itself  into  the  shape  of  an 
entire  Hydra. 

On  the  other  hand  :  "  Cells  which  form  a  small  group  involved  in  a 
larger  group,  are  subject  to  all  the  forces  of  the  larger  group,  will  become 
subordinate  in  their  structural  arrangements  to  the  larger  group,  will  be 
co-ordinated  into  a  part  of  the  major  whole,  instead  of  co-ordinating 
themselves  into  a  minor  whole  ";  hence,  the  cellular  mass  which  buds 
out  in  place  of  a  lobster's  lost  claw  gradually  assumes  the  form  of  a  claw, 
that  is  to  say,  it  has  its  parts  so  moulded  as  to  complete  the  structure  of 
the  organism. 

It  is  thus  evident  that  the  organism,  as  a  whole,  exercises  such  con- 
trolling power  over  the  newly  forming  part,  as  to  make  it  a  reproduction 
of  its  predecessor. 

Structurally  regarded,  the  new  formation  of  repair  closely  resembles 
that  of  similarly  situated  tumours  ;  and  between  the  reparative  and  neo- 


CANCER  AND  TUMOUR  GROWTH  221 

plastic  processes  there  is  obviously  an  affinity — such  differences  as  exist 
being  in  degree  rather  than  in  kind.  Indeed,  the  grand  difference  lies 
in  this  :  that  whereas  the  new  growth  of  repair  is  definitely  limited  and 
merely  suffices  to  replace  what  has  been  lost,  the  pathological  new  growth 
knows  no  such  bounds.  In  the  latter  case,  the  normal  subordination  of 
the  local  process  to  the  specific  hereditary  tendency  of  the  whole,  has 
been  diminished  or  has  ceased  to  exist.  Such  a  local  abnormality  of 
growth  may  then  acquire  a  fixed  character,  becoming  incapable  of 
further  change — except  within  the  limits  imposed  by  its  acquired  char- 
acter— and  thus  a  tumour  is  formed. 

It  has  now  been  clearly  established  by  the  criterion  of  mitosis,  that 
the  new  formation  of  repair  is  produced  by  the  active  growth  and  pro- 
liferation of  the  tissue  elements  of  the  affected  part,  in  which  leucocytes 
and  other  cellular  elements  ab  extra  are  not  essentially  concerned. 

It  has  also  been  ascertained  that  the  rapidity  of  proliferation  in  patho- 
logical regeneration,  is  greatly  in  excess  of  that  by  which  the  normal  wear 
and  tear  is  made  good. 

By  the  same  method  it  has  likewise  been  determined,  that  reparative 
processes  are  most  prone  to  arise  and  are  most  efficient,  in  those  tissues 
where  cells  capable  of  growth  and  proliferation  most  abound. 

It  has  also  been  proved  that  the  reparative  process,  like  tumour 
formation  and  the  growth  ab  ovo — of  which  latter  it  is  but  a  modified 
superinduced  repetition  in  partibus — is  independent  of  nervous  (trophic) 
and  vascular  influences  (inflammation  etc.). 

As  in  the  course  of  normal  development,  cell  derivatives  of  the  different 
blastodermic  layers  are  never  transformed  into  each  other ;  so,  in  the 
reparative  new  formation,  no  such  metamorphosis  ever  occurs.  Hence, 
no  structures  of  new  and  specific  type  are  to  be  found  in  the  new  forma- 
tion of  repair ;  whose  elementary  constituents,  as  a  rule,  resemble  those 
of  the  physiological  tissues  both  genetically  and  histologically. 

Such  at  least  appears  to  be  the  state  of  affairs  in  the  highest  organisms  ; 
but,  in  the  lower  kinds,  as  in  the  Hydra,  no  such  distinction  is  apparent. 

It  seems  probable  that  the  tissues  of  all  organisms  are  constantly 
being  destroyed,  in  the  normal  exercise  of  their  functions  ;  and  that  a 
certain  capacity  for  such  physiological  repair  as  is  necessary  for  making 
good  these  losses,  is  inherent  in  all  organisms. 

Thus,  at  certain  periods  of.  the  year,  many  animals  by  a  spontaneous 
and  natural  process  lose  certain  parts  of  their  body,  which  are  subse- 
quently renewed,  e.g.,  the  fall  of  the  stag's  horn,  the  moulting  of  birds, 
the  shedding  of  the  cuticle  of  serpents  and  the  shell  of  Crustacea  ;  while 
holothurians,  regenerate  the  digestive  tube,  after  its  voluntary  expul- 
sion etc. 

Similarly,  under  pathological  conditions,  wounds  heal,  fractured  bones 
are  repaired,  and  lost  parts  may  be  regenerated. 

This  property  is  possessed  by  mankind  and  the  higher  animals  in  but 
a  very  limited  degree  ;  but  its  perfection  in  some  of  the  lower  animals  is 
truly  astonishing. 

Moreover,  reparative  processes  are  proportionally  much  greater  in 
the  young  than  in  the  old  of  all  species,  being  greatest  of  all  in  the 


222  THE  NATURAL  HISTORY  OF  CANCER 

early  embryo  ;  and  their  efficacy  gradually  diminishes  with  advancing 
life. 

Hence  the  larvae  of  amphibians,  which  present  many  parts  that  in 
other  animals  are  developed  only  in  the  embryo  state,  have  also  greater 
powers  of  regeneration  than  the  perfect  animals  ;  and  in  the  larvae  of 
insects  lost  parts  are  often  reproduced,  which  in  the  perfect  insects 
cannot  thus  be  replaced. 

The  various  parts  and  organs  of  animals  are  also  diversely  endowed 
in  respect  to  this  faculty,  e.g.,  lizards  regenerate  the  tail,  but  not  the 
limbs  etc. 

The  general  law  to  which  these  processes  conform,  is  identical  with 
that  which  holds  for  reproduction  in  general ;  that  is  to  say,  it  is  greatest 
where  organization  is  lowest,  and  it  almost  disappears  where  organization 
is  highest. 

It  also  appears  as  if  the  capacity  for  repair  were  inversely  related, 
to  the  amount  of  energy  consumed  in  the  growth  and  development  of  the 
individual,  and  in  maintenance  of  the  same. 

Thus,  when  an  animal  so  low  in  the  organic  scale  as  the  Stentor,  is 
divided  transversely  into  two  or  three  parts,  each  of  these  grows  into  a 
complete  Stentor ;  and  this,  even  when  the  slices  removed  are  only 
half  a  millimetre  thick.  It  appears,  therefore,  as  if  each  of  the  units 
of  which  a  Stentor  is  composed,  is  capable  of  regenerating  the  whole 
organism. 

Even  among  animals  much  higher  in  the  organic  scale,  such  as  the 
polypes,  similar  phenomena  are  met  with.  Thus,  the  experiments  of 
Trembley  with  Hydra  show,  that  when  this  creature  is  divided  longi- 
tudinally or  transversely,  or  when  small  portions  are  merely  cut  out  of  its 
body,  in  all  such  cases  the  separated  fragments  grow  into  perfect  polypes. 
Even  when  the  creature  was  cut  up  into  as  many  small  pieces  as  possible, 
-each  of  these  became  a  pprfect  Hydra ;  by  methods  of  this  kind,  from  a 
single  polyp  Trembley  produced  fifty,  each  of  which  grew  into  a  perfect 
individual. 

In  this  connexion  the  question  naturally  arises,  as  to  how  small  a 
portion  of  a  metazoon  organism  may  contain  the  force  necessary  for  the 
reproduction  of  the  entire  individual  ?  In  the  case  of  Hydra,  it  appears 
as  if  almost  any  minute  group  of  cells,  severed  from  the  perfect  organism, 
sufficed  for  this  purpose. 

In  other  lowly  organized  beings,  the  power  of  reproducing  new 
individuals  is  not  merely  manifested  by  separated  portions  of  almost 
any  part  of  the  organism  ;  but,  in  some  cases,  subdivision  even  to  the 
ultimate  morphological  units,  does  not  destroy  this  power — isolated 
structural  units  are,  in  fact,  adequate  for  this  purpose. 

In  like  manner,  as  recent  experimental  researches  have  shown, 
each  of  the  cells  (blastomeres)  into  which  in  the  higher  organisms  the 
fertilized  germ  divides,  also  retains  all  the  properties  requisite  for  pro- 
ducing the  entire  organism  ;  and  this  is  so  even  up  to  the  eight-  or  sixteen- 
cell  stage  (Wilson,  Driesch,  Zoja  etc.).  Moreover,  pieces  excised  from 
globular  blastulae  before  invagination,  have  grown  into  perfect  larvae  ; 
.and  Roux  found  that  half  embryos,  evolving  from  detached  blastomeres 


CANCER  AND  TUMOUR  GROWTH  223 

of  the  frog's  egg,  finally  regenerated  more  or  less  completely  the  missing 
half. 

It  appears  to  me  that  facts  of  this  kind,  which  can  easily  be  multiplied, 
contradict  Weismann's  theory,  as  to  there  being  specific  distinction 
between  somatic  and  germ  cells. 

Among  other  experiments  on  Hydra,  Trembley  divided  polypes 
longitudinally,  when,  in  less  than  an  hour,  each  half  had  rolled  itself  and 
united  the  cut  edges,  so  as  to  constitute  each  a  fresh  polyp  ;  he  likewise 
divided  them  transversely,  and  having  brought  the  divided  halves 
together,  found  that  before  the  close  of  the  day  they  had  firmly  united. 

In  like  manner,  he  even  succeeded  in  causing  the  anterior  and  posterior 
halves  of  two  different  polypes  to  unite  ;  and  the  resultant  polyp  then 
budded  and  produced  young  polypes,  both  above  and  below  the  line  of 
union. 

Longitudinal  narrow  bands  cut  out  of  the  body  of  Hydra,  too  slender 
for  their  borders  to  unite  to  form  a  tube,  nevertheless  regenerated  com- 
plete polypes,  the  digestive  canal  being  formed  by  the  development  of 
a  new  cavity  in  the  substance  of  the  separated  fragment. 

Here  I  must  mention  a  remarkable  fact  :  several  experimenters  have 
found  that  completely  everted  polypes  still  continue  to  flourish — ecto- 
dermal  cells  quickly  taking  on  endodermal  functions,  notwithstanding 
their  obvious  morphological  differentiations. 

Imperfect  division  produced  polypes  with  two  or  more  heads  : 
Trembley  slit  one  into  seven  pieces,  leaving  them  connected  by  the  root, 
and  the  Hydra  became  seven-headed  ;  he  cut  off  the  seven  heads,  and 
they  soon  sprang  up  again.  By  laying  open  a  polyp  longitudinally,  and 
then  notching  it  in  different  directions,  he  produced  a  compound,  arbor- 
escent, plant-like  animal  with  many  heads  and  tails. 

It  was  specially  noticed  that  these  experimentally-produced  polypes 
grew  much  larger,  and  were  far  more  prolific,  .than  those  that  had  never 
been  cut ;  but,  the  supervention,  of  gemmation,  markedly  retarded  the 
regeneration  after  injury.  Warmth  favoured,  and  cold  retarded  it. 

In  such  cases  as  the  foregoing,  the  processes  of  regeneration  and  repro- 
duction by  gemmation  are  seen  to  be  identical. 

Tubularians  and  many  other  hydroids,  can  regenerate  the  "  head  " 
(i.e.,  hypostome,  mouth  and  tentacles),  after  decapitation. 

Planarians  also  possess  regenerative  capacity  in  a  high  degree. 
Duges  saw  from  eight  to  ten  new  individuals  formed,  from  sections  of  a 
single  animal ;  and  it  has  been  observed,  that  these  creatures  sometimes 
reproduce  themselves  spontaneously,  in  a  similar  way.  When  the  head 
is  damaged  they  regenerate  a  new  one. 

In  the  higher  actinozoa,  half  an  individual  will  grow  into  a  complete 
new  being  ;  and  star-fishes,  such  as  Nais,  may  be  cut  into  thirty  or  forty 
pieces,  each  of  which  will  regenerate  a  new  individual. 

In  the  common  earth-worm,  if  the  anterior  segments  as  far  back  as  the 
fifth  are  cut  off,  the  rest  of  the  body  will  regenerate  the  lost  parts,  which 
comprise  cephalic  nerve  centre,  mouth,  stomach  etc.  ;  and  this  kind  of 
regeneration  has  been  known  to  occur,  as  many  as  five  times  in  suc- 
cession. 


224  THE  NATURAL  HISTORY  OF  CANCER 

Two  pieces  of  different  earth-worms  that  have  been  transversely 
severed,  when  brought  into  apposition,  may  grow  together,  and  so  form 
a  new  worm  (Landois). 

When,  however,  worms  are  longitudinally  divided,  each  half  dies. 

Snails  can  regenerate  parts  of  the  head,  including  tentacles  and  eyes, 
provided  that  the  cerebral  ganglion  is  not  injured. 

In  insecta,  arachnida  and  Crustacea,  entire  organs  such  as  extremities, 
maxillae,  antennae,  eyes  etc.,  may  "of  ten  be  reformed  after  loss,  provided 
that  their  matrix  survives. 

In  crustaceans  the  power  of  regenerating  lost  limbs  is  highly  developed  ; 
thus,  if  the  entire  leg — except  the  minute  pair  of  proximal  segments — is 
broken  off,  a  new  leg  develops  from  the  short  stump  at  the  next  casting 
of  the  shell.  In  like  manner,  if  the  eye  of  a  crab  is  excised,  without 
injuring  the  optic  ganglion,  a  normal  eye  is  regenerated. 

As  we  ascend  in  the  scale  of  organization  this  power,  though 
diminished,  is  still  considerable. 

Among  the  vertebrata,  in  the  case  of  fishes,  regenerative  capacity  is 
generally  believed  to  be  comparatively  deficient ;  but,  it  is  known  that 
fishes  can  reproduce  lost  fins — especially  the  caudal  fin. 

Far  greater  reparative  powers  are  possessed  by  amphibians.  In 
many  of  these  the  regeneration  of  an  entire  limb  or  a  tail,  occurs  readily  ; 
and  this  even  several  times  over,  although  with  decreasing  completeness. 
Spallanzani  cut  off  the  legs  and  tail  of  a  salamander  six  times,  and 
Bonnett  eight  times,  successively  ;  and  they  were  reproduced.  In  these 
animals  the  lower  jaw,  when  damaged,  is  also  reformed,  provided  the 
stump  is  left.  As  the  observations  of  Gotte,  Fraisse,  and  Wendelstadt 
show,  when  the  fore-limb  of  a  newt  (Triton)  is  amputated  between  the 
shoulder  and  elbow,  not  only  is  the  lost  portion  of  the  humerus  formed 
afresh  ;  but  the  radius,  ulna,  and  all  the  bones  of  the  wrist  and  hand,  are 
regenerated  accurately,  even  as  regards  the  number  of  segments.  It 
seems  hardly  credible  that  such  a  complex  of  structures  could  be  repro- 
duced, merely  by  the  co-operation  of  the  local  proliferating  cells,  without 
the  agency  of  some  integrative  force  to  direct  the  process  in  accordance 
with  the  specific  hereditary  tendency  of  the  whole. 

In  these  regenerative  processes,  the  developmental  changes  are 
modelled  after  those  of  the  normal  ontogeny  ;  and,  in  the  one,  as  in  the 
other  case,  each  specific  tissue  element  only  reproduces  its  own  kind  of 
cells.  Hence,  the  regenerative  process  always  proceeds  from  the  injured 
part — remains  of  the  severed  periosteum,  endosteum  etc.,  being  essential 
for  the  process  ;  so  that,  when  the  limb  is  disarticulated  at  the  shoulder 
girdle  and  the  bones  are  uninjured,  the  latter  are  not  reproduced. 

In  the  Triton,  Blumenbach  has  seen  the  eye,  with  cornea,  iris  and  lens, 
regenerated  within  the  space  of  a  year  ;  in  comparatively  recent  times, 
Wolff,  Mueller  and  others,  having  removed  the  lens  of  the  eye  of  larval 
salamanders,  found  that  it  was  perfectly  regenerated. 

The  skin  of  amphibians  is  readily  regenerated  after  considerable  areas 
of  it  have  been  destroyed  ;  and  this  reproduction  comprises  not  only  the 
whole  epidermis,  but  also  the  various  glands  and  tegumentary  sense 
organs  (Fraisse). 


CANCER  AND  TUMOUR  GROWTH  225 

Only  the  larvae  of  the  tailless  batrachians  (frogs  etc.),  and  not  the 
adults,  are  capable  of  reproducing  lost  members  ;  but  regeneration  is  so 
complete  in  frog  tadpoles,  that  when  the  tail  is  cut  off,  it  is  reproduced, 
together  with  the  notochord. 

The  tail  of  a  lizard  is  soon  restored  after  it  has  been  cut  off  ;  but,  as 
compared  with  the  original  tail,  the  new  one  is  structurally  defective  in 
several  respects.  Thus,  instead  of  the  segmented  vertebral  axis,  it  often 
happens  that  only  an  unseg'mented  cartilaginous  tube  is  formed,  with  no 
trace  of  notochord  ;  and,  instead  of  the  spinal  cord,  only  an  epithelial 
tube  is  reproduced,  which  gives  off  no  nerves  :  moreover,  the  scales  of 
the  regenerated  tail  are  often  markedly  different  from  those  of  the 
original  one.  Lizards  are  unable  to  regenerate  lost  limbs  ;  as  also  are 
chelonians,  and  crocodiles. 

In  such  instances  of  regeneration  as  the  foregoing,  the  newly  formed 
part  is  always  very  like  its  prototype  ;  but,  I  must  now  mention  that 
the  lost  part  is  fairly  often  replaced  by  a  structure  different  from  the 
original  (heteromorphosis).  These  heteromorphic  growths  are  of  special 
interest,  as  constituting  a  connecting-link  between  the  new  formations 
of  repair,  and  tumours. 

I  have  already  called  attention  to  the  fact  that,  in  pathological  re- 
generation, the  rapidity  of  the  growth  greatly  exceeds  the  rate  of  the 
corresponding  physiological  process  ;  and  it  was  also  mentioned,  that 
polypes  produced  from  dissevered  fragments  of  Hydra  grow  much  larger, 
and  are  far  more  prolific,  than  those  which  have  never  been  cut.  In 
accordance  with  these  indications,  we  find  that  redundancy  is  the  pre- 
dominant feature  of  these  heteromorphic  manifestations.  Thus,  the 
regenerated  rays  of  star-fish  are  often  bifurcated,  or  present  supernu- 
merary parts. 

Loeb  found  that  when  a  tubularian  stem  is  cut  off  at  both  ends  and 
inserted  in  sand,  with  the  oral  end  buried,  a  new  head  is  then  regenerated 
from  the  free  end,  which  was  formerly  the  aboral  end.  When  such  a 
piece  was  suspended  in  water  by  its  middle,  a  new  head  then  formed  at 
each  end  ;  while  when  both  ends  were  buried,  neither  regenerated.  This 
shows  that  the  regenerative  process  may  be  modified  by  external  con- 
ditions. 

On  excising  the  stomach  and  ventral  nerve-cord  of  the  earth-worm f 
after  having  removed  the  ventral  halves  of  the  fourth,  fifth  and  sixth 
segments,  Weldon  noted  that  a  new  head  grew  out  of  the  gap,  producing 
an  extraordinary  double-headed  monster. 

Duges  found  that  planarians,  notched  in  the  oral  region,  regenerated 
with  two  heads  ;  and,  when  similarly  treated  at  the  opposite  end,  two 
tails  resulted. 

In  a  crayfish,  whose  nipping  claw  had  been  irregularly  amputated, 
Maggi  saw  a  double  claw  form  in  its  place  ;  and  in  other  crustaceans 
similar  happenings  have  been  noted. 

Among  amphibians,  many  instances  of  this  kind  of  anomaly  have 
been  met  with  :  in  the  axolotl  of  his  aquarium,  Vulpian  saw  a  bitten-off 
extremity  regenerated,  and  at  the  same  time  a  redundant  digit  formed  ; 
in  certain  tritons  the  same  occurrence  has  been  noted  ;  while  Piana 

15 


226  THE  NATURAL  HISTORY  OF  CANCER 

caused  polydactylism  in  these  creatures,  by  notching  the  carpus  or  tarsus 
with  scissors. 

In  frogs,  which  as  a  rule  do  not  regenerate  lost  limbs,  redundant  limb- 
like  structures  have  several  times  been  seen  to  spring  from  the  stump  of 
an  extremity  removed  by  operation. 

By  cutting  off  the  tail  of  salamanders,  lizards  etc.,  and  notching 
the  stump,  Loeb  and  others  saw  double  and  even  multiple  tails  form. 

It  has  also  been  remarked  that  when  the  amputated  tail  of  a  lizard  is 
reproduced,  the  scales  of  the  regenerated  part  are  unlike  those  of  the 
original  organ,  resembling,  indeed,  those  seen  only  in  certain  ancestral 
forms.  This  experience  recalls  the  somewhat  similar  heterotopia  met 
with  in  certain  galls,  as  previously  mentioned.1 

The  experiments  of  embryologists,  at  very  early  developmental  periods 
have  yielded  results  of  similar  import  to  the  foregoing  :  thus,  by  ligatur- 
ing the  nascent  medullary  plate  of  an  evolving  triton  germ.  Spemann 
saw  a  new  head  form,  from  the  anterior  end  of  the  posterior  part  of  this 
medullary  plate,  which  was  just  as  perfect  as  if  it  had  evolved  from  the 
anterior  part  of  the  undamaged  plate,  as  in  the  normal  course  of  ontogeny. 
It  is  thus  evident,  that  all  the  complicated  structures  concerned  in  the 
head,  can  be  evolved  from  parts,  which — if  development  had  proceeded 
normally — would  not  have  participated  in  the  formation  of  head  struc- 
tures. It  may  be  inferred  from  these  experiments,  that  each  blastomere 
or  group  of  blastomeres  of  the  evolving  germ  has  the  power,  when 
isolated,  of  forming  a  new  individual. 

It  seems  to  me  that  the  neoplastic  process  is  a  phenomenon  of  the 
same  order,  as  these  heteromorphic  new  formations  of  regeneration.  In 
both  cases  the  essence  of  the  process  is  that,  at  certain  points,  more 
intense  cell  growth  and  proliferation  sets  in  than  elsewhere.  The  differ- 
ence between  them,  is  merely  one  of  degree — the  emancipation  of  the 
proliferating  cells  from  the  control  of  the  whole  organism,  being  greater 
in  the  latter  than  in  the  former  case.  The  precise  nature  of  the  resulting 
structure  seems  to  be  determined  by  the  particular  relations  which  each 
part  has  with  the  environment,  either  habitually  in  the  individual  or 
occasionally  in  the  race. 

It  accords  with  this,  as  I  have  previously  indicated,2  that,  in  the 
higher  animals  and  in  mankind,  many  instances  are  known  in  which 
malignant  and  other  tumours  have  developed  directly  from  the  new 
formation  of  repair. 

In  the  highest  animals  and  in  mankind,  lost  parts  are  never  regene- 
rated :  in  these,  it  is  only  single  tissues  and  their  derivatives  that  are 
reproduced  ;  but,  their  wounds  heal  readily,  broken  bones  are  repaired, 
and  in  other  ways  reparative  processes  are  active. 

It  is,  however,  alleged  that  supernumerary  digits  have  been  partially 
reformed  after  amputation,  even  in  human  beings  ;  and  the  occasional 
hetero-morphic  formation  of  imperfect  nails  on  the  stumps  of  normal 
fingers  after  amputation,  seems  to  be  an  outcome  of  the  same  tendency 
in  a  slight  degree. 

According  to  J.  Y.  Simpson,  in  early  embryonic  life,  some  power  of 

1  Chapter  VI.  2  Chapters  V.  and  XI. 


CANCER  AXD  TUMOUR  GROWTH  227 

reproducing  lost  parts  may  be  met  with  even  in  mankind  ;  and  he  claims 
to  have  demonstrated  several  instances  of  the  reproduction  of  rudi- 
mentary digits,  after  the  amputation  of  limbs  in  utero  by  bands,  etc. 

Of  like  import  is  the  recurrence  of  subungual  exostosis  of  the  great 
toe,  when  the  matrix  of  the  new  formation  is  not  thoroughly  extirpated  ; 
for,  as  I  have  elsewhere  shown,1  this  new  formation  is  in  its  nature  akin 
to  digital  redundancy  at  its  minimum. 


The  Reparative  Capacity  of  the  Human  Tissues. 

In  human  tissues,  the  reparative  process  conforms  to  the  same  laws 
as  those  which  apply  to  regeneration  in  general ;  thus,  this  capacity  is 
least  in  the  highly  specialized  tissues  (e.g.,  muscle  and  nerve),  and  greatest 
in  the  comparatively  undifferentiated  (e.g.,  the  epithelial  and  connective. 

Since  the  discovery  of  "  mitosis  "  as  a  criterion  of  the  proliferative 
activity  of  the  cells,  it  has  .become  possible  to  determine  accurately  both 
the  intensity  and  the  duration  of  tissue  repair,  and  to  trace  its  histogenesis. 
By  this  method  it  has  been  proved,  that  the  new  formation  of  repair 
is  the  product  of  the  proliferation  of  pre-existing  tissue  cells  ;  and  not  of 
leucocytes  from  the  adjacent  bloodvessels,  as  was  formerly  believed. 

Studies  of  this  kind  have  shown,  that  in  some  tissues  the  constituent 
cells  continue  to  multiply  throughout  the  life  of  the  individual  (dementi 
labili)  ;  or,  at  any  rate,  up  to  some  time  after  birth  (elementi  stabili)  ; 
and  these,  as  Bizzozero  has  indicated,  repair  their  losses  with  great 
completeness.  Such  tissues  comprise  the  epithelial — whether  disposed 
as  a  covering  or  in  glandular  arrangement — connective  tissue  in  general, 
unstriped  muscle,  bloodvessels,  periosteum,  bone  etc.  These  are  the 
tissues  of  which  the  matrix  of  histioid  tumours  are  composed. 

In  another  group  of  tissues,  multiplication  of  the  cells  by  mitosis 
ceases  in  early  embryonic  life,  before  their  elements  have  assumed 
specific  character  (elementi  perenni)  ;  these  (which  comprise  the  striped 
muscles  and  nerve  tissues)  never  regenerate  completely,  and  hardly  ever 
originate  malignant  tumours. 

The  process  of  tissue  repair  is  modelled  after  the  same  plan  as  the 
process  of  tissue  development  in  ontogeny,  of  which  it  is  but  a  modified 
superinduced  repetition  :  in  both  cases,  proliferation  of  the  tissue  elements, 
and  not  inflammation,  is  the  real  starting-point,  while  bloodvessels  and 
nerves  are  at  first  absent. 

In  all  these  respects,  the  analogy  between  the  reparative  new  for- 
mation and  tumour  growth  is  very  striking  ;  and,  as  we  have  already 
seen,  tumours  sometimes  arise  directly  from  these  reparative  new 
formations. 

It  has  lately  been  shown  by  Loeb,2  Fischer,3  and  others,  that  all  the 
essential  histological  features  of  malignancy  are  reproduced  in  the 
behaviour  of  the  epidermis,  during  the  heading  of  wounds.  Thus,  the 
epithelium  on  each  side  of  superficial  cutaneous  wounds  was  found  to 

1  Bristol  Medico-Chirurgical  Journal,  March,  1904. 

2  Johns  Hopkins  Hospital  Bulletin,  January,  1898. 

3  Munch,  med.  Woch.,  1906,  Bd.  liii.,  S.  2042. 

15—2 


228  THE  NATURAL  HISTORY  OF  CANCER 

fuse  into  syncytial  masses,  whence  branching  processes  budded  out,  not 
only  bridging  the  gap,  but  also  growing  downwards,  into  and  through 
the  subjacent  clot,  penetrating  the  underlying  damaged  tissues  and  even 
cartilage,  just  as  happens  in  cancer.  Indeed,  it  is  suggested  that  this 
penetrative  quality  of  the  ingrowing  cells  is  due — in  the  one  as  in  the 
other  case — to  enzyme  action.  However  this  may  be,  it  is  now  evident 
that  there  is  not  only  anatomical,  but  also  physiological  resemblance,  in 
the  two  processes. 


CHAPTER  X 
THE  MICROBIC  THEORY  OF  CANCER 

ALTHOUGH  it  appears  to  me,  for  reasons  set  forth  in  previous  chapters, 
that  the  influence  of  extrinsic  factors  is  no  more  necessary  to  account  for 
the  origin  and  growth  of  a  tumour,  than  it  is  to  account  for  the  origin  and 
growth  of  a  tooth  or  a  hair  ;  yet,  I  think  it  is  a  mistake  to  deny  on 
a  priori  grounds,  the  possibility  of  irritants  db  extra  inciting  tumour 
germs  to  such  proliferative  activity,  as  may  eventuate  in  tumour 
growth. 

No  one  has,  indeed,  ever  succeeded  in  intentionally  producing  any 
kind  of  tumour  by  such  extrinsic  agencies  ;  although,  by  means  of  this 
kind,  as  we  have  already  seen,  somatic  cells  may  be  incited  to  prolifera- 
tion, which  sometimes  results  in  the  formation  of  tumour-like  pseudo- 
plasms  of  malignant  aspect,  of  which  I  shall  have  more  to  say  in  the 
sequel.  Among  such  extrinsic  agents,  microbes  and  their  toxins  hold  an 
important  place. 

I  cannot,  therefore,  concur  with  Ziegler,1  when  he  says  :  "  All  the 
biological  characters  of  tumours  testify  against  their  parasitic  origin." 
My  objection  to  the  doctrine  of  extrinsic  tumour  pathogenesis  is  rather 
based  upon  the  fact,  that  the  balance  of  available  evidence,  on  con- 
sideration of  the  ensemble  of  the  subject,  seems  to  be  decidedly  against 
it.  Moreover,  as  the  phenomena  of  the  disease  can  be  so  much  better 
explained  without  invoking  the  aid  of  this  hypothesis,  as  a  primary 
setiological  factor,  it  seems  to  me  that  we  ought  to  leave  it  aside,  until 
much  stronger  evidence  in  its  favour  is  forthcoming  than  any  at  present 
available.  The  need  for  so  doing  becomes  all  the  more  obvious  when  we 
recollect,  as  in  the  course  of  my  narrative  I  shall  proceed  to  show,  that  of 
the  many  pathologists  who  claim  to  have  discovered  the  cancer  parasite, 
all  are  in  disaccord  as  to  its  nature  ;  thus,  it  has  been  ascribed  to  bacteria 
of  many  different  kinds,  to  various  protozoan  parasites,  to  diverse  kinds 
of  fungi,  and  various  other  lowly  parasites  and  pseudo-parasites.  The 
truth  is,  most  pathologists  are  so  strongly  prepossessed  in  favour  of  the 
conception  that  nearly  all  diseases,  not  obviously  due  to  some  gross 
external  cause,  must  be  of  parasitic  origin,  that  it  is  difficult  to  get  them 
to  regard  this  malady  from  any  other  standpoint.  Hence,  although  the 
microbe  of  cancer  has  not  yet  been  discovered,  the  microbic  theory  is 
still  the  order  of  the  day. 

Of  course,  the  mere  fact  that  no  specific  cancer  microbe  has  yet  been 
discovered,  does  not  per  se  prove  its  non-existence  for,  of  many  maladies 

1  Munch,  med.  Woch.,  1898,  Bd.  xlv.,  S.  312. 
229 


230  THE  NATURAL  HISTORY  OF  CANCER 

almost  certainly  parasitic  (e.g.,  small-pox,  vaccinia,  measles,  scarlet  fever, 
syphilis  etc.),  the  same  may  be  said ;  and,  as  is  within  the  recollection  of 
every  one,  the  microbe  of  tubercle  was  only  discovered  in  1882. 

Neither  can  the  absence  of  contagion  per  se  be  regarded  as  proof  of 
the  non-existence  of  a  cancer  microbe  ;  for  some  maladies,  although 
demonstrably  of  parasitic  origin,  are  not  transmissible  by  ordinary  con- 
tagion (e.g.,  malaria,  coccidial  disease  of  rabbits  etc.). 

One  of  the  most  remarkable  properties  of  malignant  tumours,  is  their 
power  of  continuous  autonomous  growth  and  development  (individuality), 
upon  which  their  so-called  parasitism  depends.  It  is  by  virtue  of  this 
property  that  they  persist,  and  tend  to  increase  indefinitely.  Inflam- 
matory pseudo-plasms,  on  the  other  hand,  after  a  time  tend  to  disappear  ; 
nevertheless,  there  are  exceptions,  for  some  pseudo-plasms,  such  as 
mycosis  fungoides,  as  well  as  certain  tuberculous,  actinomycetic,  syphi- 
litic and  some  other  pseudo-plasms,  are  often  very  persistent. 

A  striking  feature  about  cancerous  growths,  is  the  great  morphological 
difference  that  obtains  between  them,  according  to  the  localities  whence 
they  originate.  What,  for  instance,  can  be  more  divergent  in  this  respect, 
than  the  appearances  presented  on  microscopical  examination,  by  sections 
of  cancer  from  such  different  parts  as  the  breast,  the  stomach,  and  the 
skin  ?  We  learn  from  such  examinations,  that  cancerous  growths  are 
sufficiently  organized,  to  present  unmistakable  histological  resemblance 
to  the  structures  whence  they  originate.  Herein  they  differ  from  most 
inflammatory  pseudo-plasms,  which  present  the  same  granulomatous 
structure,  no  matter  in  what  part  of  the  body  they  arise.  When,  how- 
ever, epithelial  elements  are  included  in  proliferating  granulomatous 
tissue,  they  are  often  thereby  incited  to  grow  and  proliferate,  of  which 
"  Jensen's  tumour  "  is  an  example  in  mice  ;  and,  in  humanity — among 
many  such  instances — uterine  "  erosions  "  may  be  cited. 

The  great  resemblance  always  noticeable  between  primary  and 
secondary  cancerous  growths  is  a  phenomenon  of  similar  import,  which 
cannot  be  accounted  for  on  the  basis  of  inflammation  and  micro-organisms. 
It  is  impossible  to  conceive  a  valid  explanation  of  such  conditions, 
without  the  presence  of  cells  capable  of  reproducing  their  like  by 
growth,  multiplication,  and  organization.  I  am  aware  that  microbists 
make  light  of  this  objection,  alleging  that  the  emigrant  cancer  cells 
carry  their  parasites  with  them  to  their  new  habitat,  where  the 
said  parasites  cause  a  repetition  of  the  initial  morbid  process.  But, 
independently  of  the  fact  that  cells  invaded  by  parasites  tend  to 
lose  their  power  of  growth  and  proliferation,  it  never  seems  to  have 
occurred  to  the  authors  of  this  suggestion,  how  unlikely  it  would  be  for 
microbes  transported,  for  instance,  into  the  liver,  to  produce  in  this 
organ  the  typical  structure  of  breast  cancer.  Surely,  if  the  secondary 
lesions  were  really  due  to  microbes,  these  might  be  expected  to  incite 
the  liver  cells  to  malignant  growth  ;  and  so  to  cause  the  formation  of 
typical  hepatic  cancer.  As  Moxon  has  sagely  remarked  :  "  The  first 
cancer  which  appears  has  a  likeness  to  the  part  in  which  it  appears,  and 
the  secondary  cancers  arising  from  it  have  the  likeness  of  that  first 
cancer  ;  and,  those  that  doubt  that  they  came  from  that  first,  cancer, 


THE  MICROBIC  THEORY  OF  CANCER  231 

must  show  us  why  they  have  that  likeness."  In  this  connexion,  Waring's  x 
experiments  are  of  interest,  for  they  show  that  the  cellular  elements  of 
the  secondary,  as  well  as  those  of  the  primary  growths,  in  cancer  of  the 
pancreas  and  stomach,  produce  the  same  ferments  etc.,  as  the  normal 
secretory  cells  of  these  parts. 

Thus  may  be  explained  the  great  resemblance  always  noticeable 
between  the  primary  and  secondary  growths,  the  significance  of  which 
it  is  impossible  to  ignore.  In  short,  these  phenomena  clearly  imply  that 
the  disease  centres  in  the  tumour  cells  themselves  ;  and  not  in  any 
extraneous  condition.  Thus,  this  peculiarity  of  malignant  tumours, 
marks  them  off  from  microbic  pseudo-plasms,  more  definitely  than  any 
other  single  item. 

In  like  manner,  the  peculiar  age  and  sex  incidence  of  the  malady,  and 
the  occurrence  of  congenital  cases,  testify  against  its  parasitic  origin. 

Such  then  are  some  of  the  reasons  for  regarding  the  microbic  theory  of 
cancer  as  improbable. 

Before  a  disease  can  properly  be  called  parasitic,  the  parasite  must 
be  found,  isolated  ;  and,  the  disease  it  is  alleged  to  cause,  must  be  repro- 
duced by  its  inoculation.  Judged  by  this  standard,  the  microbe  of 
cancer  has  not  yet  been  discovered  ;  for,  none  of  the  bodies  hitherto 
described  as  such,  comply  with  these  requirements.  Of  the  numerous 
researches  undertaken  during  the  last  quarter  of  a»century  with  a  view  to 
finding  it,  all  have  proved  abortive.  Where  now  are  the  specific  cancer 
microbes  of  Rappin,  Freire,  Scheuerlen,  Schill,  Francke,  Lampiazi- 
Rubino,  Sanarelli,  Kiibasoff  and  Doyen  ;  of  Pfeiffer,  Thoma,  Wickham, 
Sjobring,  Soudakewitch,  Ruffer,  Walker,  Plimmer,  Adamkiewicz, 
Korotneff,  Juergens,  Bosc,  Leyden  and  Schaudinn,  Schuller,  Gaylord, 
Feinberg,  Robertson  and  Wade  ;  of  Russell,  Sanfelice,  Niessen,  Bra, 
Monsarrat,  Leopold,  0.  Schmidt  etc.  ?  One  after  another,  the  alleged 
discoveries  of  this  recalcitrant  organism,  have  ended  only  in  disappoint- 
ment. The  negative  results  of  numerous  implantation  and  other  similar 
experiments,  as  previously  detailed,  point  to  the  same  conclusion. 

In  short,  the  evidence  hitherto  adduced  as  to  the  existence  of  a  specific 
cancer  microbe,  is  altogether  inconclusive  ;  hence,  if  there  really  is  any 
microbe,  from  whose  presence  in  the  body  cancer  must  necessarily 
result,  I  can  only  conclude  that  it  altogether  transcends  present  ex- 
perience. 

As  soon  as  the  microscope  had  revealed  to  pathologists  the  wonders 
of  the  infinitely  minute,  the  medical  world  expected  that  some  definite 
morphological  element  would  soon  be  found  distinctive  of  cancer.  The 
search  for  specific  cancer  elements,  although  discouraged  by  J.  Miiller 
and  Virchow,  was  keenly  pursued  by  others  ;  and  Lebert  soon  announced 
that  he  had  discovered  the  specific  cancer  cell.  When  this  claim  proved 
untenable,  the  turn  of  the  nucleus  came  and  its  mode  of  division  (mitosis)  ; 
while  lately,  as  we  have  already  seen,  the  centrosome  has  been  similarly 
regarded.  The  minutest  cytological  investigations  having,  however, 
failed  to  reveal  the  long-expected  specific  element  of  cancer  ;  and,  chemical 
researches  in  this  direction  having  proved  equally  futile,  it  remained  for 
1  Journal  of  Anatomy,  October,  1893,  p.  142. 


232  THE  NATURAL  HISTORY  OP  CANCER 

the  microbists  to  complete  the  search.  It  is  to  this  popular  demand  for 
a  materies  morbi,  to  this  desire  for  some  tangible  and  concrete — if  empirical 
— explanation  of  the  phenomena  of  malignancy,  that  the  microbic  theory 
of  cancer  really  owes  its  vogue.  Limited  to  non-malignant  tumours,  it 
would  probably  have  gained  but  few  adherents  ;  hence  the  battle  as  to 
its  relevancy,  has  centred  round  the  pathogenesis  of  malignant  tumours. 

These  the  microbic  theory  regards  as  the  product  of  "  chronic  inflam- 
mation," consequent  on  "  irritation,"  resulting  from  the  presence  in  the 
tissues,  or  in  the  cells,  of  living  organisms  or  their  toxins.  It  attributes 
not  only  the  initiation  of  the  abnormal  growth,  to  parasitic  activity  ; 
but  also  its  progress  and  continuance.  Thus  regarded,  malignant  tumours 
would  be  classed  with  the  infective  granulomata. 

Thus  the  conception  of  the  microbists  as  to  cancer  genesis,  is  an 
exact  reproduction  of  the  doctrine  of  Broussais,  so  extensively  held  at  the 
beginning  of  the  last  century,  plus  microbes. 

It  is  presumed  that  the  special  action  of  the  parasites  in  causing 
malignancy,  is  mainly  due  to  the  fact  that  they  often  penetrate  into  the 
constituent  cells  of  the  tumour  and  dwell  there,  as  it  were  in  symbiosis — 
the  union  being  so  intimate  that  as  the  parasite  proliferates,  so  also  does 
the  nucleus  of  its  epithelial  host.  It  is,  however,  a  remarkable  fact — - 
which  none  of  those  who  have  investigated  the  subject  have  yet  explained 
— that  the  nucleus  ofc  a  cancer  cell  invaded  by  "  parasites,"  always 
appears  to  be  in  a  state  of  degenerative,  rather  than  of  proliferative, 
activity.  It  accords  with  this,  that  these  "  parasite-containing  "  cells 
are  very  inapt  at  proliferation,  or  do  not  proliferate  at  all. 

As  to  the  life-history  of  this  hypothetical  parasite,  nothing  is  yet 
known  ;  but,  on  a  priori  grounds,  it  is  presumed  to  have  some  analogy 
with  that  of  the  tubercle  bacillus  etc.,  beginning  with  a  primary  lesion  at 
the  site  of  inoculation,  and  being  followed  by  generalization.  Metchnikoff , 
however,  maintains  that  it  should  be  classed  with  the  miasmatic  diseases, 
and  that — like  malaria — it  is  probably  propagated  by  spores  formed 
outside  the  body,  the  incubation  period  varying  from  a  few  days  to  a 
few  years. 

In  order  to  test  the  validity  of  such  statements,  investigators  have 
for  some  time  been  very  busy  in  endeavouring  to  discriminate  and 
isolate  these  supposed  parasites  ;  to  get  pure  cultures  of  them  ;  and  by 
inoculation  to  reproduce  the  disease  in  animals,  afterwards  recovering 
the  "  parasites  "  from  the  latter.  Such  is  the  aim  of  all  recent  researches 
on  this  question. 

It  is  necessary  to  insist  on  the  rigid  enforcement  of  these  precautions 
before  arriving  at  any  definite  conclusions  ;  for  only  thus  can  we  avoid 
being  deceived,  by  what  Pasteur  calls  the  besetting  weakness  of  medical  in- 
vestigators, viz.,  their  unfortunate  tendency  to  generalize  by  anticipation. 

As  Crookshank  says  :  "  It  is  of  very  little  value  merely  to  detect  or 
artificially  to  cultivate  a  microbe  associated  with  disease.  We  must 
endeavour  to  establish  its  exact  relationship  with  the  morbid  process  ; 
and  the  determination  of  the  true  pathogenic  value  of  a  microbe  is  beset 
with  many  fallacies."  In  the  sequel,  the  necessity  for  regarding  this 
word  of  caution  will  be  abundantly  manifest. 


THE  MICROBIC  THEORY  OF  CANCER  233 

It  is  a  well-recognized  rule  in  pathology — although  more  honoured 
in  the  breach  than  in  the  observance — that  familiarity  with  the  minute 
anatomy  of  a  part  and  of  its  various  morbid  variations,  should  precede 
the  special  study  of  any  supposed  pathological  novelty. 

It  must  be  confessed  that  the  original  investigators  of  the  so-called 
parasites  of  cancer  entered  on  their  quest,  very  badly  equipped  in  this 
respect.  They  came  armed  with  novelties — with  new  microscopes  of 
unprecedented  magnifying  power,  with  new  stains  of  great  complexity, 
and  with  new  technique  of  equal  elaboration.  Instead  of  first  testing 
these  inventions  on  normal  tissues,  on  known  morbid  conditions,  and  on 
known  microbic  diseases,  they  rushed  straight  away  to  the  study  of  the 
minute  anatomy  of  cancer — a  disease  that  had  never  before  been  investi- 
gated with  this  degree  of  elaboration.  Although  manifesting  unfamiliarity 
with  the  latest  findings  in  normal  cytology,  they  never  hesitated  as  to 
the  interpretation  of  the  most  obscure  and  complicated  appearances  in 
cancer  cytology.  As  to  their  acquaintance  with  the  life-history  and 
histological  appearances  of  microbes,  well — not  to  put  too  fine  a  point 
upon  it — this,  as  a  rule,  evidently  left  much  to  be  desired.  Approaching 
a  subject  of  this  degree  of  complexity,  thus  imperfectly  equipped,  the 
need  for  control  experiments  was  sufficiently  obvious  ;  yet,  as  the  pub- 
lished reports  show,  such  experiments  were  seldom  made.  If,  under  these 
circumstances,  the  strange  sights  thus  brought  to  light  in  this  terra 
incognita  were  often  misinterpreted,  what  wonder  ?  The  hunt  for 
"  cancer  parasites  "  has  rightly  been  stigmatized  by  Schaudinn,  as  one  of 
the  most  melancholy  chapters  in  biological  investigation ;  hence,  in  dealing 
with  this  kind  of  publication,  we  must  never  forget  the  need  for  criticism. 

Passing  now  to  the  dominant  object  of  the  present  chapter,  which  is 
to  review  the  work  done  as  to  the  "  parastiology  "  of  cancer,  it  may  at  the 
outset  be  mentioned,  that  microbes  first  began  to  be  heard  of  in  this 
connexion  early  in  the  seventies  of  the  nineteenth  century. 

But,  long  before  this,  as  previously  mentioned,1  similar  views  had  been 
prevalent.  At  a  later  period,  in  the  eighteenth  century,  cancer  was 
regarded  by  John  Hunter  as  the  product  of  a  morbid  poison,  which 
either  arose  spontaneously  or  was  derived  from  the  contagion  of  similar 
disease  ;  and  he  compared  it  with  small-pox,  tubercle,  syphilis,  and 
similar  diseases. 

In  1809,  cancer  was  described  by  R.  Carmichael 2  as  :  "A  parasitic 
disease  due  to  animalculae  produced  by  generatio  equivocal  He  thought 
that  carbonate  of  iron  cured  the  disease,  by  destroying  the  animalculse. 


Bacteria. 

In  the  modern  revival,  it  was  among  the  schizomycetes  that  specific 
cancer  microbes  were  first  alleged  to  have  been  discovered. 

Even  as  early  as  1880,  Nepveu3  had  described  the  presence  of  bac- 

1  Chapter  VIII. 

2  An  essay  on  the  effects  of  Carbonate  and  other  preparation  of  Iron  on  Cancer,  etc. 
Dublin,  1809. 

3  Qaz.  Hebd.  de  Med.,  etc.,  1888,  p.  278  ;  also  C.  R.  Soc.  de  Biol.,  1887,  t,  iv.,  p.  756. 


234  THE  NATURAL  HISTORY  OF  CANCER 

teria  in  tumours  of  this  kind  ;  and  Lebard  1  again  called  attention  to 
this  subject  in  1885. 

Rappin  2  in  1886,  and  SchiU  3  in  1887,  demonstrated  the  existence  of 
dipiococci  in  carcinomatous  and  sarcomatous  neoplasms  ;  and  claimed 
that  these  were  the  cause  of  the  disease. 

They  soon  had  numerous  imitators  in  Francke,4  Scheuerlen,5  Freire,6 
Lampiazi-Rubino,7  Sanarelli,8  Kiibasoff,9  and  others.  As,  however, 
none  of  them  really  succeeded  in  reproducing  the  disease  by  inoculation 
with  pure  cultures,  the  futility  of  their  claims  for  setiological  specificity 
soon  became  apparent  ;  and  they  have  since  been  entirely  abandoned, 
and  have  now  passed  out  of  recollection. 

At  the  time  of  its  publication  in  1887,  however,  Scheuerlen's  pro- 
nouncement made  a  great  stir.  He  claimed  to  have  solved  the  cancer 
problem  by  the  discovery  of  a  specific  bacillus,  and  to  have  reproduced 
the  disease  in  animals  by  inoculating  them  with  pure  cultures  of  it.  His 
method  was  that  of  cultivating  the  substance  of  mammary  cancers  upon 
solid  media,  comprising  sterilized  ascitic  and  hydrocele  fluids.  On  the 
third  day,  a  growth — in  the  form  of  a  colourless  film,  becoming  yellowish 
later — usually  appeared,  which  the  microscope  showed  to  consist  of  short 
bacilli  and  spores.  The  latter — which  stained  readily  with  ordinary 
reagents — he  often  found  in  the  .dried  juice  of  cancers  ;  the  former,  he 
could  not  demonstrate  in  stained  histological  sections,  but  he  found 
them  in  fresh  cancer-juice.  Bitches  inoculated  in  the  mammary  region 
with  pure  cultures  of  these  bacilli,  developed  there  in  the  course  of  a 
fortnight  tumours  the  size  of  a  walnut.  When  the  animals  were  killed— 
a  month  after  inoculation — these  tumours  were  found  to  be  epithelial 
new  formations,  in  which  the  spores  of  the  bacilli  could  be  easily  dis- 
tinguished. 

Senger,10  Baumgarten  n  and  others,  investigating  Scheuerlen's  bacillus- 
shortly  afterwards,  showed  that  it  was  nothing  but  a  potato  bacillus,  one 
of  the  several  kinds  of  organism  that  grow  readily  on  slices  of  potato. 
It  was   therefore   a   mere   epiphyte,  having  no  setiological  relation   to 
malignant  disease. 

Shattock  and  Ballance,12  attempting  to  get  cultures  from  fragments 
of  fresh  non-ulcerated  mammary  cancers,  removed  with  aseptic  precau- 
tions and  carefully  transferred  to  tubes  of  beef  peptone  jelly,  beef  peptone 
agar-agar,  and  solidified  blood-serum,  concluded — since  no  growth  took 
place  in  any  of  the  tubes — that  these  tumours  contained  no  microbes 
capable  of  cultivation.  Similar  experiments  with  sarcomatous  and 

1  Arch.  Gen.  de  Med.,  1885,  t.  L,  p.  413. 

2  "  Recherches  sur  1'etiologie  des  tumeurs  malignes,"  Xantes,  1887. 

3  Deutsche  med.  Woch.,  1887,  S.  1034. 
*  Munch,  med.  Woch.,  1887,  Xo.  4. 

5  Deutsche  ined.  Woch.,  1887,  Xo.  48,  S.  1033. 

6  Bev.  d.  Cursos.  Prat.  e.  Theor.  d.  Fac.  d.  Med.  d.  Bio  de  Janeiro,  1889,  p.  73. 

7  Li  Riforma  Med.,  Xapoli,  1888,  vol.  iv.,  p.  20. 

8  Ibid.,  Roma,  1889,  p.  356. 

9  Wien.  med.  Presse,  1890,  Bd.  31,  Xos.  29  to  33. 

10  Berlin,  klin.  Woch.,  1888,  No.  10,  S.  185. 

11  Cent.  f.  Bakt.,  etc.,  1888,  Bd.  iii.,  S.  397. 

12  Transactions  of   the  Pathological  Society,  London,  1887,  vol.   xxxviii.,   p.   412  ; 
also  ibid.,  1888,  vol.  xxxix.,  p.  409. 


THE  MICROBIC  THEORY  OF  CANCER  235 

lipomatous  tumours,  gave  the  same  negative  results.  Moreover,  they 
found  that  fragments  of  malignant  and  other  tumours,  aseptically 
treated,  could  easily  be  kept  sterile  for  considerable  periods,  just  as  could 
bits  of  the  healthy  tissues. 

Verneuil,1  having  noticed  the  frequency  with  which  his  operation 
wounds  became  septically  infected,  after  the  removal  of  cancerous 
tumours  in  which  there  were  areas  of  softening,  made  special  bacterio- 
logical examination  of  these  foci ;  and  found  that  they  teemed  with 
various  kinds  of  bacilli  and  micrococci,  several  species  often  being  present 
in  the  same  tumour. 

In  the  same  year,  Zahn  2 — by  cultivation  experiments — showed  that 
bacteria  may  abound  in  the  metastases  of  cancer,  even  when  the  latter 
have  no  direct  communication  with  the  surface  of  the  body. 

Hauser  3  thinks  we  need  not  be  surprised  to  find  bacteria  in  ulcerated 
malignant  growths  ;  since,  under  these  circumstances,  the  conditions 
met  with  are  highly  favourable  to  their  growth  and  development. 
When  microbes  are  found  in  metastatic  growths,  Hauser  believes  that 
they  are  carried  there,  by  tumour  elements  detached  from  the  primary 
focus. 

Kiibasoff 4  in  carcinomata  of  the  stomach  found  short,  thick  bacilli, 
which  showed  active  movements  when  incubated.  In  various  culture 
media — such  as  gelatin,  agar-agar  etc. — they  formed  scale-like  colonies, 
which  did  not  liquefy  gelatin.  Guinea-pigs,  rabbits,  cats  and  dogs,  when 
inoculated  with  pure  cultures,  died  in  a  comparatively  short  time.  On 
post-mortem  examination  nodular  tumours — which  are  described  by 
Kiibasoff  as  presenting  the  structure  of  cancer — were  found  in  various 
internal  organs.  He  regarded  this  bacillus  as  the  true  cause  of  the 
disease. 

Schiitz,5  by  means  of  various  aniline  dyes,  was  able  to  discriminate 
various  forms  of  bacteria  in  ulcerated  cancer  of  the  lip  ;  but  these  he 
regarded  as  mere  epiphytes. 

Richet 6  found  septic  bacteria  often  present  in  cutaneous  carcinomata  ; 
and  extracts  made  from  tumours  of  this  kind  seemed  to  possess  a  special 
virulence  of  their  own.  Thus,  while  injections  of  the  extract  of  fresh 
non-ulcerated  cancers  had  no  toxic  effect  whatever  on  animals,  a  few 
cubic  centimetres  of  the  same  preparation  from  an  ulcerating  cancer, 
caused  convulsions  and  death. 

Several  investigators  have  reported  the  existence  of  bacteria  in  the 
blood  of  patients  with  malignant  tumours  ;  and  some  have  claimed  for 
these  bodies  special  setiological  significance. 

Hayem,7  however,  who  has  specially  studied  the  various  alterations 
in  the  form  of  the  blood-corpuscles  in  malignant  and  other  diseases,  con- 
cludes that  the  pseudo-parasitic  bodies  are  due  to  degenerative  corpuscular 
changes  (microcytosis,  poikilocytosis,  fragmentation  etc.). 

Rev.  de  Chir.,  1889,  t.  ix.,  p.  793. 

Arch.  f.  path.  Anat.,  1889,  Bd.  cxvii.,  S.  209. 

"  Des  cylinder  Epitheliom  des  Magens  "  etc.,  Jena,  1890. 

Wien.  med.  Presse,  1890,  Bd.  xxxi.,  S.  1145  et  seq. 

Cent.  f.  Bakt.,  etc..  1890,  Bd.  ix.,  No.  21,  S.  702. 

C.  R.  de  I'Acad.  des  Sci.,  1895.  ii..  Xo.  17.  7   "  Du  Sang,"  Paris,  1889. 


236  THE  NATURAL  HISTORY  OF  CANCER 

Moty  x  found  micrococci  in  the  blood  of  nearly  all  the  patients  with 
sarcoma,  examined  ad  hoc  by  him.  In  cultures  they  developed  as  a 
narrow,  pointed  or  festooned  band,  surrounded  by  small  isolated 
colonies. 

Maragliano  2  examined  the  blood  of  thirty-three  patients  with  cancer 
of  various  parts  of  the  body.  In  nine  cases  bacteria  were  present- 
mostly  different  kinds  of  staphylococci.  In  all  these  instances,  the 
tumours  showed  some  signs  of  disintegrative  processes  ;  but,  in  none 
of  the  patients  was  there  any  pyrexia,  or  other  indication  of  septic 
infection.  In  patients  with  non-ulcerated  tumours,  he  was  never  able 
to  detect  any  bacteria  in  the  blood. 

The  latest  champion  of  the  bacterial  origin  of  cancer  is  Doyen,  of 
Paris  ;  who,  at  a  meeting  of  the  French  Academy  of  Medicine,  held  in 
December,  1901,  announced  the  discovery  of  a  new  "  cancer  microbe,"' 
which  he  called  Micrococcus  neoformans.  He  maintains  that  this  microbe 
— which  is  a  diplococcus — is  constantly  present  in  cancerous  tumours,  and 
may  be  best  demonstrated  in  sections  stained  with  picro-carmine  and 
violet ;  and  that  he  has  been  able  to  isolate  it,  and  cultivate  it,  in  special 
gelatin-bouillon  media.  It  presented  in  pairs,  and  in  short  chains.  He 
found  that  cultures  were  more  easily  obtained  from  affected  lymph-glands 
and  secondary  growths,  than  from  the  primary  tumour.  He  claims  to 
have  produced  cancerous  tumours  in  various  animals,  by  inoculating 
them  with  pure  cultures  of  the  microbe  ;  and  also  to  have  succeeded  in 
preparing  a  sterilized  solution  of  its  toxins — attenuated  in  a  special 
manner — which,  when  subcutaneously  injected  into  those  affected  with 
the  disease,  retards  its  progress. 

In  a  subsequent  publication,3  Doyen  claims  with  this  solution,  up  to 
September  30,  1904,  to  have  completely  cured  42  out  of  242  patients 
treated,  and  to  have  markedly  benefited  many  others. 

A  committee  of  the  Societe  de  Chirurgie,  which  was  subsequently 
appointed  to  report  on  Doyen's  therapeutic  methods  and  results,  has 
lately  issued  an  adverse  report 4 — the  unanimous  conclusion  being,  that 
the  treatment  has  no  favourable  action  on  cancer  :  "  During  the  five 
months  in  which  we  have  examined  all  the  cases  which  M.  Doyen  wished 
to  show  us,  we  have  not  seen  a  single  instance  of  amelioration." 

Jacobs  and  Geets  5  have  since  published  experiences,  which  tend  to 
support  Doyen's  thesis  ;  but  Wright  and  others,  who  have  repeated 
their  experiments,  have  failed  to  verify  their  results. 


General  Conclusions  as  to  Bacteria. 

From  such  items  as  the  foregoing,  the  following  conclusions  may  be 
drawn  : — 

1.  Malignant  tumours  are  singularly  prone  to  bacterial  infection, 
owing  to  their  feeble  vitality,  which  is  a  consequence  of  defective  sanguini- 

1  Bull.  Med.,  October  14,  1894.  2  Gaz.  degli  Ospitali,  January  13,  1901. 

3  "  Etiologie  et  Traitement  du  Cancer,"  Paris,  1904. 

4  C.  E.  Soc.  de  Chir.,  July  12,  1905.  5  C.  R.  Roy.  Acad.  de  Med.  Bdgique,  1906. 


THE  MICROBIC  THEORY  OP  CANCER  237 

fication.  The  organisms  usually  present  under  these  circumstances,  are 
such  as  may  be  commonly  met  with  in  corresponding  normal  parts  of  the 
body,  e.g.,  micrococci,  diplococci,  streptococci,  staphylococci,  various 
large  and  small  rod-shaped  bacilli  etc. 

2.  In  their  young  and  nascent  condition,  non-ulcerated  malignant 
tumours  are  quite  free  from  bacteria. 

3.  Although  many  kinds  of  bacteria  may  find  a  suitable  habitat  in 
malignant   tumours,   none   of  these   organisms   fulfil   the  requirements 
necessary  for  the  establishment  of  their  setiological  specificity,  as  "cancer 
microbes." 

Protozoa. 

Just  as  the  movement  in  support  of  the  bacterial  origin  of  malignant 
tumours  was  on  the  wane,  a  new  movement  arose  ascribing  the  causation 
of  the  disease  to  parasitic  protozoa. 

More  than  half  a  century  previously,  Hake  x  had  noticed  that  cancer 
cells  often  contained  certain  rounded,  hyaline,  spore-like  bodies,  which 
he  regarded  as  psorospermial  parasites.  Some  years  later,  Virchow2 
also  examined  these  bodies  ;  but  he  concluded  that  they  were  the  out- 
come of  endogenous  cell  formation  and  degenerative  changes. 

About  the  year  1889,  several  cytologists  (Pfeiffer,  Thoma  and  Darier} 
announced  that  they  had  discovered  similar  bodies — which  they  regarded 
as  psorospermial  parasites — in  cancer  cells  from  various  parts  of  the 
body.  Thus  the  old  controversy,  as  to  the  significance  of  these  bodies, 
was  revived  ;  and  this  question  soon  became  the  cynosure  of  pathological 
eyes,  for  the  problem  of  the  origin  of  cancer  seemed  to  concentre  in  it. 

It  appears  that  Pfeiffer,3  who  had  specially  studied  coccidiosis  in  the 
rabbit,  was  one  of  the  earliest  to  publish  an  account  of  parasitic  sporozoa 
in  human  cancer.  On  teasing  fragments  of  a  malignant  melanotic 
tumour,  on  the  warm  stage  of  a  powerful  microscope,  he  saw  plasmodia 
in  amreboid  movement ;  and  observed  that  they  resembled  one  of  the 
microsporidia,  which  infest  the  roots  of  cabbages  and  other  cruciferae — 
the  Plasmodiophara  brassicce. 

At  about  the  same  time  Thoma  4  described  certain  endocytes,  which 
he  found  in  the  protoplasm  and  nucleus  of  cancer  cells  ;  and  he  main- 
tained that  they  were  coccidia. 

The  announcement  by  Darier  5  in  the  same  year,  of  the  discovery  of 
coccidial  parasites  in  cases  of  "  Paget's  disease"  of  the  breast,  contributed 
not  a  little  to  the  general  interest  which  the  subject  had  excited. 

Among  the  earliest  supporters  of  the  protozoan  origin  of  these  endo- 
cytes, besides  those  above  mentioned,  were  Malassez,  Albarran,  Wickham, 
Metchnikoff,  Soudakevitch,  Ruffer,  Foa  and  Cattle  ;  while  their  non- 
parasitic  nature  was  just  as  strenuously  upheld  by  Borrel,  Cornil,  Gibbes, , 
Klebs,  Ribbert,  Pianese,  Delepine,  Sroebe,  Virchow,  Kanthack  and  others, 

1  "  A  Treatise  on  Varicose  Capillaries,"  etc.,  London,  1839. 

2  Arch.  f.  path.  Anat.,  Bel.  i.,  SS.  107,  130,  483  ;  also  Bd.  iii.,  S.  197. 

3  "  Die  Protozoen  als  Krankhoitserreger,"  Jena,  1891. 
*   Fortschritte  der  Med..  1889,  Bel.  vii..  S.  413. 

6  C.  R.  Soc.  de  Biologic.  April  13,  1889. 


238  THE  NATURAL  HISTORY  OP  CANCER 

The  work  of  these  early  investigators  was  entirely  histological  ;  and, 
it  soon  became  apparent,  that  they  meant  to  class  as  cancer  parasites, 
every  rounded  body  that  was  not  obviously  either  an  epithelial  cell,  a 
nucleus,  a  leucocyte,  or  a  red  blood-globule.  Indeed,  there  were  some 
among  them  (Pfeiffer,  Adamkiewicz,  Jackson  Clarke  etc.),  who  went 
to  much  greater  lengths,  maintaining  that  the  constituent  elements  of 
cancerous  tumours  were  merely  masses  of  parasitic  protozoa  ;  and,  not 
epithelial  cells,  as  generally  believed.  In  spite  of  some  opposition  from 
the  more  moderate  parasitologists,  the  investigation  was  continued  in 
this  spirit,  until  Soudakevitch  l  and  Ruffer 2  for  the  first  time  clearly 
defined  precisely  what  was  meant  by  the  term  "  cancer  parasite."  They 
thus  discriminated  from  the  immense  variety  of  so  -  called  parasites, 
certain  small,  rounded  endocytes,  each  of  which  contained  a  nucleus, 
surrounded  by  voluminous  protoplasm,  itself  circumscribed  by  a  distinct 
capsule.  With  the  Ehrlich-Biondi  stain  the  nucleus  assumed  a  copper- 
red  colour,  while  the  surrounding  protoplasm  coloured  light  greenish  or 
bluish,  the  capsule  taking  a  decided  reddish  tint.  Immediately  around 
the  nucleus  a  clear  zone  was  noticeable  ;  and,  in  "  parasites  "  of  a  certain 
size,  fine  radial  striation  was  often  seen.  All  bodies  different  from  these, 
such  as  had  been  described  by  previous  observers  as  cancer  parasites, 
Ruffer  rejected  as  such,  declaring  that  they  were  only  pseudo-parasites, 
having  no  aetiological  relationship  whatever  with  malignancy. 

The  precise  nature  and  significance  of  the  bodies  thus  discriminated, 
still  remain  to  be  determined.  Shattock  and  Ballance  3  were  among  the 
earliest  of  those  who  undertook  experiments,  with  the  object  of  deter- 
mining whether  cancer  could  be  produced  by  inoculating  animals  with 
psorospermise  from  the  rabbit's  liver  etc.,  as  the  statements  of  Darier 
and  Wickham  implied.  Rabbits,  monkeys,  dogs  and  rats,  were  employed 
for  this  purpose.  The  method  was  to  scarify  the  ear,  by  making  one  or 
more  long  incisions  on  its  inner  aspect ;  and,  after  bleeding  had  ceased, 
to  rub  into  the  wounds  fresh  psorospermial  material  from  the  liver  of  a 
recently  killed  rabbit.  This  was  followed  by  the  formation  of  linear 
elevations  along  the  incision  tracks,  owing  to  reparative  hyperplasia  ; 
but,  otherwise,  the  results  were  always  negative.  This  was  the  case, 
even  when  large  quantities  of  psorospermial  material  were  injected  into 
the  jugular  vein  of  dogs  etc. 

They  concluded  that,  until  animals  or  human  beings  had  been  experi- 
mentally infected  by  inoculation,  with  cultures  made  from  Paget's 
disease  or  from  cancerous  tumours,  nothing  could  be  taken  as  proved,  as 
to  there  being  any  causal  relation  between  psorospermiae  and  cancer. 

According  to  Adamkiewicz,4  the  infectivity  of  cancer  is  so  well  estab- 
lished, that  its  parasitic  nature  may  be  regarded  as  a  certainty.  He 
maintains  that  the  constituent  cells  of  cancerous  tumours  are  not  epithelial 
cells,  as  is  generally  believed,  but  parasitic  organisms.  "  A  cancer  cell 
is  not  an  epithelial  cell,  but  an  animal — a  protozoon — especially  a  cocci- 
cdium  (Coccidium  sarcolytes}"  Since  all  parasitic  microbes  produce 

1  Ann.  de  I'Inst.  Pasteur,  1892,  No.  3,  p.  145 ;  also  ibid.,  Xo.  8,  1892,  p.  545. 

2  Transactions  of  the  Pathological  Society,  London,  1893,  vol.  xliv.,  p.  209. 

3  Ibid.,  189L  vol.  xlii.,  p.  377. 

4  "  Untersuchungen  iiber  den  Krebs,"  Wien,  1893,  etc. 


THE   MICROBIC  THEORY  OF  CANCER  239 

toxins,  Adamkiewicz  believes  that  there  must  also  be  a  special  cancer 
toxin  ;  and  this  he  claims  to  have  discovered  in  a  substance,  termed  by 
him  ''  cancroin,"  which  he  has  extracted  from  malignant  tumours.  He 
finds  that  this  substance  is  chemically  akin  to  neurin — "  tri-methyl- 
vinyl-ammonium-hydroxide. ' ' 

By  implanting  brain  substance  and  other  tissues  from  cancer  patients, 
into  divers  regions  of  various  animals,  Adamkiewicz  claims  to  have 
caused  in  them  a  specialized  intoxication,  owing  to  the  action  of  this 
toxin.  Xo  cultures  of  any  parasitic  organism  were  made. 

Geissler,  Kopfstein  and  others,  who  repeated  these  experiments, 
were  unable  to  confirm  Adamkiewicz's  results. 

By  subcutaneously  injecting  cancer  patients  with  cancroin,  Adam- 
kiewicz also  claims  to  have  cured  many,  even  after  only  a  few  weeks' 
treatment.  It  must  be  stated,  however,  that  those  who  have  had  the 
best  opportunities  of  closely  following  his  cases,  have  failed  to  appreciate 
his  alleged  curative  results  ;  and,  generally,  his  statements  inspire  no 
confidence. 

Delepine  *  found  that  the  psorospermia-like  bodies  met  with  in 
malignant  tumours  failed  to  respond  to  any  of  the  chemical  tests,  which 
give  definite  reactions  with  the  psorospermial  parasites  of  the  rabbit's 
liver.  He  also  failed  to  find  in  the  so-called  "  cancer  parasites,"  any  of 
the  developmental  forms  met  with  in  the  parasitic  psorospermise  of 
rabbits. 

By  inoculating  interlamellar  films  of  water,  serum,  nutrient  gelatin, 
and  other  fluids,  with  psorospermiae  from  the  rabbit's  liver,  he  obtained 
cultures  of  these  parasites,  and  succeeded  in  following  their  development 
through  various  stages.  By  this  method,  the  changes  occurring  in 
individual  psorospermiae  could  be  followed  for  weeks. 

Delepine  suggests  that  the  protozoa-like  bodies  of  malignant  tumours, 
should  be  studied  in  the  same  way  ;  when,  if  similar  changes  were  observed 
in  them,  the  doubts  as  to  their  real  nature  might  thus  be  removed. 
Attempts  subsequently  made  in  this  direction  by  Delepine  and  Cooper, 
failed  to  elicit  any  indications  of  multiplication  and  growth  when  the 
so-called  cancer  parasites  were  substituted,  in  the  experiments,  for 
psorospermige  from  the  rabbit's  liver. 

D'Arcy  Power,2  a  supporter  of  the  protozoan  theory,  has  also  attacked 
the  problem  from  an  experimental  standpoint.  He  brought  mucous 
surfaces — of  rabbits  rats,  etc. — that  had  for  some  time  been  kept  in  a 
state  of  chronic  irritation,  into  contact  with  cancerous  tissues,  when  the 
former  became  infected  with  "  cancer  bodies  ";  but,  cancerous  tumours 
could  never  be  thus  produced.  Only  a  few  experiments  were  made  ; 
and  there  were  no  control  observations  with  healthy  epithelial,  instead 
of  cancerous  tissues,  so  that  these  results  are  by  no  means  convincing. 

In  a  subsequent  publication  (1894),  Power  admits  the  validity  of  this 
criticism  ;  for,  he  there  says  :  ''  It  may  be  that  the  "  cancer  bodies  "  are 
merely  phases  in  the  degeneration  of  cells.  .  .  .  They  are  met  with  in 
normal  epithelium,  which  has  been  slightly  irritated  ;  and,  I  am  there- 

1  Transactions  of  the  Pathological  Society,  London,  1891,  vol.  xlii.,  p.  371. 

2  British  Medical  Journal,  1893,  vol.  ii.,  p.  832  ;  also  ibid.,  1894,  vol.  ii.,  p.  638. 


240  p^HE  NATURAL  HISTORY  OF  CANCER 

fore  boun(}ri  to  confess  myself  an  unbeliever,  in  any  of  the  "  cancer  bodies  " 
which  ly^ave  yet  been  discovered." 

K'-urloff1  found  an  organism,  which  appeared  to  be  identical  with 
thr,o  Rhopalocephalus  canceromatosus  of  Korotneff,  in  a  primary  cancer  of 
/"the  skin  of  the  dorsum  of  the  hand  of  a  man  aged  eighty. 

In  a  further  series  of  experiments,  Shattock  and  Ballance2  again 
endeavoured  to  get  cultures  of  the  "  parasitic  protozoa  "  of  human 
malignant  tumours.  Under  the  impression  that  it  might  be  necessary 
for  the  hypothetical  parasites  to  pass  through  some  lower  organism,  in 
order  to  acquire  infective  properties  for  man  and  animals,  they  fed  worms, 
kept  in  sterilized  sand  and  water,  with  bits  of  mammary  cancer.  These 
were  devoured,  but  the  worms  unfortunately  died  soon  afterwards,  owing 
to  the  sterility  of  the  sand  depriving  them  of  all  other  nutriment.  Bits 
of  fresh  mammary  cancer  were  next  buried  in  garden  soil,  and  six  weeks 
later  these  were  exhumed  and  introduced  into  the  abdominal  cavity  of 
rats  ;  but  only  negative  results  ensued.  In  other  experiments,  fragments 
of  malignant  tumours  in  Petri  dishes  etc.,  were  introduced  into  sterilized 
sand  and  water  to  which  a  little  beef  peptone  broth  had  been  added  : 
after  variable  periods,  sand  from  the  vicinity  of  these  bits  of  buried 
tumour  was  examined  ;  but,  although  the  sand  often  teemed  with  amoebae 
and  bacteria,  no  sporozoa  were  present.  The  results  of  inoculating 
animals  with  this  sand,  and  with  bits  of  the  tumours  that  had  been 
buried,  were  always  negative. 

Searching  for  a  protective  vaccine  against  malignant  disease,  Shattock 
and  Ballance  tried  the  effect  of  subcutaneous  injections  of  50  per  cent, 
glycerine  extracts  of  cancer  and  sarcoma,  into  patients  affected  with 
inoperable  malignant  tumours  ;  but  in  no  case  did  any  improvement 
ensue. 

They  next  essayed  the  effect  of  injections  of  the  fresh  serum  of  animals, 
such  as  sheep,  which  are  naturally  but  little  liable  to  malignant  tumours  ; 
but  these  also  were  inefficacious.  The  serum  of  animals  into  whose 
circulation  cancer-juice  had  been  injected,  was  also  employed  thera- 
peutically  ;  but  without  any  appreciable  result. 

Bosc  3  endeavoured  to  get  cultures  of  the  hypothetical  psorosperms 
of  human  cancers,  by  incubating  bits  of  recently  removed  tumours  in 
ordinary  culture  media.  He  maintains  that  the  "  cancer  bodies " 
multiplied  in  these  media  ;  but,  as  he  never  even  attempted  to  inoculate 
animals  with  the  cultures,  the  value  of  his  statements  is  comparatively 
small. 

Among  those  who  continued  the  investigation  of  the  "  cancer  para- 
sites "  discriminated  by  Soudakevitch  and  Ruffer,  Plimmer4  was  one  of 
the  first  who  employed  the  experimental  methods,  that  had  been  intro- 
duced by  Sanfelice  and  the  Italian  pathologists.  He  seems  to  have  been  so 
much  impressed  by  the  results  of  these  methods,  as  even  to  doubt  the 
dictum  of  Metchnikoff,  as  to  the  protozoan  nature  of  these  bodies. 

Although   Plimmer   managed   to   demonstrate   histologically   to   his 

1  Cent.  f.  Bakt.,  etc.,  Bd.  xv.,  Nos.  10  and  11. 

2  Proceedings  of  the  Royal  Society,  1895,  vol.  lix. 

3  "  Le  Cancer,"  Paris,  1898. 

4  Proceedings  of  the  Royal  Society,  March  9,  1899  ;  also  Practitioner,  April,  1899. 


THE  MICROBIC  THEORY  OF  CAXCER  241 

satisfaction  "  cancer  parasites  "  in  almost  all  of  the  numerous  malignant 
tumours  specially  examined  ad  hoc,  he  only  once  succeeded  in  isolating 
by  artificial  culture  "  an  organism  which  in  certain  animals  was  capable 
of  causing  death,  with  the  production  of  tumours  in  various  parts." 
His  culture  medium  was  an  infusion  of  human  cancer  prepared,  just  as 
the  ordinary  beef  infusion,  with  the  addition,  after  neutralization,  of 
2  per  cent,  of  glucose  and  1  per  cent,  of  tartaric  acid. 

Guinea-pigs  inoculated  intra-peritoneally  with  these  cultures,  died  in 
from  thirteen  to  twenty  days  ;  and  on  post-mortem  examination  the 
peritoneum,  omentum,  liver,  spleen,  intestines  and  lungs,  were  found  to 
be  studded  with  small  nodules  of  endothelial  structure,  the  constituent 
cells  of  which  contained  "  organisms  "  similar  to  those  isolated  from 
the  human  cancer.  He  claims  that  these  experiments  demonstrate 
"  the  production  of  tumours  by  an  organism  isolated  from  human  cancer  "; 
which,  he  thinks,  "  may  have  a  practical  bearing  on  the  great  question 
of  the  aetiology  of  cancer."  In  some  cases  he  claims  to  have  produced  by 
inoculation,  true  malignant  epithelial  (cancerous)  tumours.  Thus,  by 
scarifying  a  rabbit's  cornea,  and  inoculating  it  with  the  sediment  of  a 
ten-days-old  culture,  he  found,  when  the  animal  was  killed  forty-eight 
hours  afterwards,  that  free  proliferation  of  the  corneal  epithelium  had 
taken  place,  and  that  these  cells  were  invaded  by  "  cancer  parasites." 
This  proliferation  spread  for  some  distance.  Plimmer  believed  that  this 
was  an  artificially  produced  cancerous  lesion.  I  certainly  think  that  he 
has  not  brought  forward  one  iota  of  evidence,  that  will  justify  such  a 
conclusion.  This  lesion  migjit  just  as  well  have  been  produced  by  the 
inoculation  of  any  irritant.  Wyss  and  others  have  shown  that  corneal 
lesions  of  all  kinds,  involving  destruction  of  surface  epithelium,  are 
quickly  followed  by  ingrowths  of  the  adjacent  epithelial  cells,  with  his- 
tological  appearances  like  cancer. 

In  numerous  other  experiments,  rabbits  and  guinea-pigs  were  inocu- 
lated intra-venously,  intra-peritoneally,  and  subcutaneously  ;  but  with 
merely  negative  results.  In  yet  other  cases,  the  only  obvious  effect  was  ; 
that  the  "  organisms  "  were  found  post-mortem  in  the  blood,  internal 
organs  etc. 

Pianese *  has  published  a  very  elaborate  study  of  the  cytology  of 
cancer,  with  special  reference  to  the  nuclear  changes  of  the  morbid  cells, 
and  to  the  so-called  parasites.  He  examined  specimens  from  fifty-five 
cancers  of  different  parts  of  the  body.  He  describes  the  mitoses  found  in 
cancers,  which  he  classifies.  Special  attention  is  given  to  the  group  of 
degenerations  which  comprises  hyalinosis,  keratohyalosis,  mucoid,  colloid, 
and  amyloid  changes  ;  and  their  relations  to  les  corps  de  Darier,  the 
sporozoa  of  Korotneff  (Rhopalocephalus  canceromatosus),  and  to  Russell's 
bodies.  Endocytes  due  to  secretory  changes  in  glandular  cancers  are 
also  studied. 

Attention  is  then  directed  to  the  nucleus  and  nucleolus  of  cancer 
cells  ;  for,  having  found  that  chromatin  often  occurred  in  these  inclusions, 
Pianese  maintained  that  many  of  them  had  a  nuclear  origin.  The 

1  "  Beitr.  z.  Histologie  und  Aetiologie  des  Carcinoma  "  (suppl.  Ziegler's  Beitr.  z- 
path.  Anat.,  Jena,  1896). 

16 


242  THE  NATURAL  HISTORY  OF  CANCER 

special  nuclear  changes  may  affect  chiefly  (a)  the  nuclein  (swelling,  diminu- 
tion, fragmentation,  degeneration)  ;  (6)  the  paranuclein  (fragmentation, 
degeneration)  ;  or  the  nucleolus  (vacuolization,  encapsulation)  ;  (c)  the 
envelope  of  the  nucleus  ;  or  (d)  the  nuclear  juice  (filamentous,  nucleo- 
plasmolysis). 

In  conclusion,  he  studied  : — (1)  hyalinosis  of  the  nucleoplasm  ; 
(2)  pseud-adipose  or  cystic  degeneration  of  the  nucleus  ;  (3)  amyloid 
degeneration  of  the  entire  cancerous  cell ;  (4)  necrosis  of  the  nucleus  ; 
and  (5)  amyloid  cancer  bodies. 

Pianese  concludes  that,  up  to  the  date  of  his  communication  (1896), 
we  had  no  evidence,  histological  or  experimental,  that  would  justify  us 
in  describing  any  of  the  numerous  "  parasites,"  such  as  have  been  figured 
and  described  as  being  found  in  cancers,  as  other  than  products  of  altera- 
tions of  the  protoplasm,  of  the  nucleus,  or  of  both  combined. 

Leyden  and  Schaudinn,1  examining  ascitic  fluid  removed  from  cancer 
patients,  made  the  interesting  discovery,  that  it  teemed  with  rhizopodia 
— organisms  that  had  never  before  been  met  with  in  the  human  body, 
except  as  parasites  of  the  gastro-intestinal  tract.  These  microbes  pre- 
sented as  amoeboid  bodies,  of  from  3  to  36  millimetres  in  diameter, 
their  shape  being  globular  or  irregularly  polygonal,  and  having  a  char- 
acteristic appearance,  which  is  compared  to  a  bird's  eye.  At  intervals 
they  emitted  processes  of  hyaline  ectoplasm,  and  the  pseudo-podia  of 
adjacent  organisms  sometimes  anastomosed.  Each  of  them  was  fur- 
nished with  a  nucleus  of  the  typical  rhizopod  type  ;  and  they  multiplied 
by  segmentation  or  gemmation,  colonies  often  being  formed.  One  of 
the  patients  above  referred  to  had  cancer  of  the  pylorus  ;  the  other  had 
an  intra-abdominal  tumour. 

When  a  drop  of  the  ascitic  fluid  or  its  centrifugalized  sediment,  was 
microscopically  examined  in  the  fresh  state,  the  organisms  were  readily 
seen,  as  above  described.  Permanent  preparations  were  also  made.  As 
to  the  possible  setiological  relation  between  these  rhizopods  and  the  con- 
comitant cancerous  disease,  the  authors  at  first  declined  to  commit 
themselves  ;  but  they  subsequently  affirmed  their  belief  that  the  organism 
is  the  specific  cancer  parasite,  although  they  were  unable  to  comply 
with  Koch's  postulates ;  and  they  have  named  it  Leydenia  gemmipara 
Schaudinn. 

The  foregoing  publication  has  been  the  starting-point  of  many  sub- 
sequent researches.  Thus  Nils  Sjobring,2  with  a  culture  medium  con- 
sisting of  nearly  equal  parts  of  sterile  ascitic  fluid  and  peptone  gelatin, 
with  the  addition  of  1-5  per  cent,  of  watery  solution  of  potash  soap  pre- 
pared with  human  fat,  and  1  per  cent,  of  cane-  or  grape-sugar,  succeeded 
in  cultivating — from  fresh  human  tumours — an  animal  organism  pre- 
senting amoeboid,  rhizopod,  and  involution  forms. 

Tubes  of  this  special  culture  medium  were  inoculated  with  pieces  of 
non-ulcerating  human  tumours,  that  had  been  aseptically  treated ; 
and  these  were  then  incubated  for  a  week  at  37°  C.  (98-6°  F.).  By  this 

1  "  Sitz.  d.  Akad.  d.  Wissenschaft  z.  Berlin,"  1896,  Bd.  xxxix.,  S.  13 ;  also  "  Uber  die 
parasitare  Theorie  in  der  Aetologie  der  Krebse,"  Berlin,  1905. 

2  Fortschritte  der  Mod.,  1890,  No.  14  ;  also  Cent.  f.  JBakt.,  etc.,  1900,  xxvii.,  S.  129. 


THE  MICROBIC  THEORY  OF  CANCER  243 

means,  from  various  carcinomata,  sarcomata,  uterine  myomata,  and 
ovarian  cystomata,  Sjobring  succeeded  in  isolating  these  rhizopod 
organisms. 

With  these  cultures  he  inoculated  eight  white  mice,  and  in  four  cases 
positive  results  were  obtained.  In  two  cases  cultures  of  human  mammary 
cancers,  subcutaneously  injected,  after  a  period  of  three  months,  are 
alleged  to  have  caused  the  formation  of  cylinder-celled  cancer  of  the 
cutaneous  sweat-glands  and  hair-follicles.  In  another  experiment,  the 
resultant  tumour  resembled  an  adenoma  of  a  sweat-gland.  In  the  fourth 
case,  a  culture  from  a  colloid  cystoma  of  the  human  ovary,  intra-peri- 
toneally  injected,  gave  rise  to  colloid  cystoma  of  the  epididymis  etc.  In 
all  of  these  animals  "  cancer  bodies,"  similar  to  those  found  in  human 
malignant  tumours,  were  demonstrated.  With  rabbits  and  guinea-pigs 
the  inoculations  gave  only  negative  results. 

In  their  initial  stage  these  "  organisms  "  presented  as  sarcous,  rounded, 
quasi-fatty  masses  ;  subsequently  pseudo-plasmodia  developed.  In  cer- 
tain forms  the  nuclear  chromatin  could  be  demonstrated,  by  aniline  blue 
staining  and  with  iron-alum-heematoxylin.  Their  development  was  like 
that  of  the  amcebosporoids  of  the  protozoa  ;  but  sexual  conjugation,  and 
the  sickle-shaped  germ,  were  absent. 

Histological  sections  of  the  artificially  produced  skin  tumours  in  mice, 
exhibited  at  the  Congress  of  German  surgeons  in  1901,  produced  a  by  no 
means  favourable  impression.  The  evidence  as  to  epithelial  new  for- 
mation, was  considered  to  be  inconclusive.  Juergeiis  could  not  recognize 
the  so-called  cancer  bodies  as  parasites  ;  and  Israel  was  of  the  same 
opinion,  maintaining  that  the  so-called  sporophoroides  and  rhizopodia 
were  nothing  but  fat  globules  and  debris. 

Max  Schiiller a  has  published  an  account  of  an  organism — of  protean 
form — which  he  detected  in  carcinomatous  and  sarcomatous  tumours, 
and  isolated  by  cultures.  His  procedure  was  that  of  incubating  bits  of 
the  fresh  tumours,  taking  care  not  to  expose  them  to  a  lower  temperature 
than  that  of  the  body.  He  discriminates  two  typical  forms  ;  of  these, 
the  more  characteristic  are  large  organisms,  three  or  four  times  the  size 
of  red  blood-corpuscles — round  or  ovoid,  refractile,  of  golden  yellow  or 
brownish  colour,  having  a  well-defined  capsule  perforated  by  numerous 
pores,  within  which  are  three  or  four  small  protoplasmic  masses,  which, 
in  the  course  of  development,  appear  to  escape  through  the  capsular  pores 
and  form  independent  organisms.  It  is  from  the  latter  that  the  smaller 
type  of  organism  is  believed  to  originate  ;  these  present  as  clear  or  finely 
granular,  rounded  cells  of  golden  colour.  These  small  forms  act  as  intra- 
cellular  parasites,  penetrating  the  tumour  cells,  even  to  their  nuclei,  where 
they  undergo  their  further  phases  of  development — identical  parasites 
being  found  in  both  the  epithelial  and  connective-tissue  forms  of  malignant 
disease. 

In  living,  hanging  -  drop  cultures,  these  organisms  present  fine 
peripheral  processes.  It  is  believed  that  the  small  types  of  organism 
develop  into  the  larger  ones. 

1  "  Die  Parasiten  im  Krebs  und  Sarkom  des  Menschen,"  Jena,  1901  ;  also  abstract  in 
Cent.  f.  Bakt.,  etc.,  1900,  Bd.  xxvii.,  S.  511. 

16—2 


244  THE  NATURAL  HISTORY  OF  CANCER 

Cultures  injected  into  the  tissues  and  organs  of  rabbits  and  other 
animals,  caused  local  proliferations,  similar  to  those  met  with  in  com- 
mencing cancer — carcinomatous  cultures  being  capable  of  producing 
sarcomatous  etc. 

Max  Schiiller  has  also  found  and  made  cultures  of  similar  organisms, 
from  the  lesions  of  acquired  and  congenital  syphilis. 

Not  a  little  sensation  was  caused  when,  in  1901,  Volcker  l  declared 
that  Max  Schuller's  large  yellow,  cancer  parasites,  were  in  reality  nothing 
but  cork  cells  ;  which  had  got  into  the  specimens,  through  the  medium  of 
the  oil  used  for  clarifying  the  same. 

According  to  Hansemann,2  the  endocytes  of  cancer  cells  are  derived 
from  many  different  sources,  which  he  enumerates  as  follows  : — (1)  De- 
generations of  cells  and  secretory  anomalies,  (2)  phagocytosis,  (3)  invagi- 
nation,  (4)  abortive  and  pathological  mitoses,  (5)  special  organs  of  cells, 
e.g.,  archoplasm  and  centrosome,  (6)  extra-cellular  hyaline  drops  (Russell's 
bodies),  and  (7)  cancer  cells  themselves. 

In  a  previous  chapter  I  have  referred  to  the  observations  of  Borrel 
and  Le  Count,  as  to  the  identity  of  Ruffer's  endocytes  with  the  archo- 
plasm and  centrosome. 

Olt 3  considers  that  the  so-called  parasites  of  cancer  are,  in  reality, 
red  blood-cells  in  various  stages  of  degeneration.  He  attempted  to  obtain 
cultures  from  cancers  from  the  horse,  dog  etc.,  using  various  media. 
The  results  were  negative.  He  concludes  : — "  From  the  fact  that  these 
supposed  parasites  are  iron-containing  bodies,  and  that  their  optical 
properties  are  very  similar  to  those  of  the  red  blood-cells,  it  may  be 
inferred  that  the  latter  are  concerned  in  their  formation."  Sjobring's 
rhizopod  parasites,  Olt  regards  as  nothing  but  particles  of  free  fat. 

Bruandet 4  by  injecting  a  solution  of  coccidia  into  the  pelvis  of  the 
kidney  of  a  rabbit,  after  having  ligatured  the  ureter  lower  down,  claims 
to  have  caused  thereby  quasi-cancerous  epithelial  changes  in  the  kidney, 
as  determined  by  histological  examination,  when  the  animal  was  killed 
about  three  and  a  half  weeks  after  the  injection. 

Gaylord5  claims  to  have  discovered  "  the  protozoan  of  cancer,"  in 
ascitic  fluid  derived  from  a  patient  with  colloid  cancer  of  the  peritoneum  ; 
which,  when  inoculated  into  animals,  produced  cancerous  tumours. 
Cultures  of  this  organism  on  Fucus  crispus  bouillon  gave  similar  results. 
He  also  found  microbes  of  this  kind,  in  various  cancerous  and  sarco- 
matous tumours  ;  and  got  pure  cultures  of  them.  In  advanced  cases, 
they  could  always  be  detected  in  the  patient's  blood,  and  in  the  internal 
organs.  With  cultures  from  these  various  sources,  many  animals  were 
inoculated  ;  and,  in  a  few  instances,  nodular  tumours  were  found  a  month 
or  so  later,  when  the  animals  were  killed.  In  an  experiment  in  which  the 
injection  was  made  into  the  jugular  vein  of  a  guinea-pig,  a  pulmonary 
nodule  was  found,  when  the  animal  was  killed  three  and  a  half  weeks 
later.  Microscopical  examination  of  this  artificially  produced  tumour, 
revealed  proliferous  cells  in  branching  columns,  which  Gaylord  interpreted 

1  Deutsche  med.  Woch.,  July  25,  1901.  2  Berlin,  klin.  Woch.,  1894,  No.  1. 

3  Deutsche  thierdrzt  Woch.,  1900,  Nos.  22  and  23. 

*  La  Presse  Mid.,  1902,  p.  400. 

6  Journal  of  the  American  Medical  Association,  1901,  vol.  cxxi.,  p.  503. 


THE  MICROBIC  THEORY  OF  CANCER  245 

as  adeno-carcinoma.  For  the  demonstration  of  this  protozoon,  Gaylord 
relies  chiefly  on  unstained  specimens — the  scrapings  of  cancerous  tumours 
etc.  He  found  the  parasites  in  every  case  of  cancer  and  sarcoma  specially 
examined,  as  well  as  in  myoxma,  fibro-adenoma,  colloid  goitre,  and  syphi- 
litic glands.  It  is  evidently  very  similar  to  the  bodies  previously  described 
by  Schaudinn  and  Sjobring,  and  to  Max  Schiiller's  "  young  forms."  In 
the  fresh  state,  Gaylord's  parasite  closely  resembled  fatty  gloubles  ; 
indeed,  it  was  only  by  finding  that  they  did  not  react  with  ether  and 
osmic  acid  as  fat  does,  that  he  was  able  to  discriminate  them  from  fatty 
aggregations.  He  next  found,  that  he  could  crack  their  edges  with  a 
cover-glass.  They  existed  in  greatest  abundance,  in  the  softened  dis- 
integrating areas  of  cancerous  tumours,  where  Plimmer  and  Ruffer  could 
never  find  parasites. 

Gaylord  maintains  that  there  is  great  resemblance  between  his  cancer 
parasites  ;  and  the  bodies  met  with  by  Pfeiffer  and  others,  in  variola 
and  vaccina,  which  are  also  believed  to  be  protozoa.  They  present  as 
pale  yellowish,  granular  bodies,  like  fat  droplets,  from  3  to  10  millimetres 
in  diameter,  large  and  small  types  being  discriminated.  By  incubating 
hanging-drop  preparations  of  fresh  cancer-juice,  derived  from  scraping 
the  tumour,  the  smaller  forms  of  the  organism  could  be  followed  in  their 
development ;  they  augmented  in  size  and  became  granular,  emitting 
pseudo-podia  and  developing  a  nucleus,  ultimately  being  converted  into 
sporiferous  sacs. 

Feinberg  l  claims,  as  the  outcome  of  histological  research  with  special 
staining,  to  have  discovered  a  new  intra-cellular  sporozoan  cancer 
parasite  (Histosporidium  carcinomatosum),  which  he  maintains — solely  on 
the  histological  appearances — is  the  true  cause  of  the  disease.  It  is  in 
the  nucleus  of  this  parasite,  and  in  its  staining  reactions,  that  Feinberg 
finds  the  distinctive  features  requisite  for  the  recognition  of  the  same. 
Outside  the  body,  he  believes  this  organism  only  exists  in  the  spore  form. 

Otto  Schmidt 2  claims  to  have  discovered  a  protozoon-like  parasite  in 
malignant  tumours,  which  he  has  cultivated  outside  the  body  ;  white 
mice,  injected  with  these  cultures,  developed  malignant  tumours.  He 
has  found  this  parasite  in  animal,  as  well  as  in  human,  malignant  tumours. 
Dead  cultures  of  this  organism,  and  the  serum  of  animals  immunized 
by  culture  inoculations,  were  found  to  exert  protective  action  against 
malignant  growths.  Schmidt  also  claims  to  have  cured  many  persons 
affected  with  cancer,  by  means  of  similar  inoculations ;  and  greatly  to 
have  benefited  still  more. 

This  supposed  cancer  specific  has  been  tested  at  the  Middlesex 
Hospital ; 3  but,  none  of  the  patients  there  treated,  derived  any  benefit 
from  the  procedure. 

It  has  been  pointed  out,  that  the  "  cancer  parasites  "  described 
by  Leyden,  Sjobring,  Schiiller,  Gaylord,  Feinberg  and  some  others, 
much  resemble  the  Plasmodiophora  brassicce,  a  parasitic  organism,  which 
causes  tumour-like  swellings  (club-root)  in  cruciferous  plants.  As  pre- 

1  Wien.  klin    Woch.,  1903,  No.  45,  S.  1235;  also  "Des  Gewebe  und  die  Ursache  der 
Krebsgeschwiilste,"  etc.,  1903. 

2  "  Mittheilung  aus  Dr.  O.  Schmidt's  Laboratorium,"  1905. 

3  Arch.  Middlesex  Hospital,  1904,  vol.  iii.  (J.  W.  G.  Myler). 


246  THE  NATURAL  HISTORY  OF  CANCER 

viously  mentioned,  Pfeiffer,  who  first  described  the  endocytes  of  cancer 
as  parasitic  protozoa,  long  ago  called  special  attention  to  this  similarity. 
This  organism  lives  symbiotically  in  the  infected  plant-cell,  its  spores 
being  found  even  within  the  nucleus  ;  and  thus  it  is  believed  that  the 
abnormal  local  cell  proliferation  is  excited,  which  results  in  the  formation 
of  the  tumour-like  excrescences.  It  is  claimed  that,  just  as  these  plant 
formations  are  caused  by  the  plasmodiophorae  ;  so  human  cancers  are 
caused  by  parasitic  intra-cellular  protozoa.  To  test  this  conception, 
Podvyssotski J  has  struck  out  a  new  line,  by  experimenting  with  this 
organism,  which  is  a  kind  of  myxo-myces.  He  inoculated  rabbits,  rats, 
guinea-pigs  etc.,  with  these  parasites,  producing  granulomatous  forma- 
tions— "  myxo-mycetic  perithelioma,"  but  not  epithelial  proliferation. 
Within  the  cells  of  these  artificially  produced  tumours,  he  found  spores 
of  the  plasmodiophora  ;  in  such  vicinities  there  were  also  many  giant 
cells,  and  evidences  of  phagocytosis.  These  nodular  formations  were, 
however,  evanescent. 

Gaylord  2  has  also  made  experiments  of  this  kind.  Thus,  with  fresh 
"  club-foot  "  material,  various  animals  were  inoculated  ;  and,  when  these 
were  killed  on  the  twelfth  day  after  the  experiment,  granulomatous 
nodules  were  found,  which  comprised  many  phagocytic  cells,  in  which 
were  spores  and  spore  cysts.  There  was  also  some  infiltration  of  the 
surrounding  tissues  with  leucocytes.  The  histological  appearances  of 
these  spores  were  often,  "  indistinguishable  from  those  of  cancer  inclu- 
sions ";  but  there  were  no  signs  of  epithelial  proliferation,  nor  of  any  struc- 
ture like  cancer.  According  to  Gaylord,  these  artificially  produced 
nodules  were  true  grafts — their  cells  being  derived  exclusively  from  the 
cells  experimentally  implanted. 

Tuboef  3  inoculated  many  animals  with  this  same  parasite ;  but  pro- 
duced nothing  at  all  like  cancer. 

Robertson  and  Wade  4  claim  to  have  proved  by  histological  methods, 
that  cancerous  tumours  comprise  intra-cellular  parasites,  which  are 
identical  with  the  Plasmodiophora  brassicce  in  its  pre-spore,  spore,  pre- 
amoeboid  and  amoeboid  stages  ;  but  much  more  minute.  The  reactions 
of  these  bodies  with  the  platinum  and  silver-gold  methods,  were  iden- 
tical with  those  given  by  the  "  club-foot  "  parasites.  They  also  claim 
to  have  grown  from  cancerous  tumours,  an  organism  which  represents 
the  post-spore  or  pre-amceboid  stage  of  a  plasmodiophora  ;  and  they 
maintain  that  this  organism  has  the  same  relation  to  cancer,  as  the 
Plasmodiophora  brassicce  has  to  "  club-foot  ";  that  is  to  say,  is  its  specific 
causative  factor.  No  inoculation  experiments  are  reported.  Alto- 
gether, the  authors'  conclusions  seem  to  go  beyond  what  is  warranted 
by  the  ascertained  facts.  In  view  of  the  cloud  of  adverse  witness  set 
forth  in  the  preceding  narrative,  as  well  as  in  what  follows,  the  futility 
of  claims  to  determine  the  nature  of  cancer  endocytes,  solely  by  histo 
logical  methods,  ought  by  this  time  to  be  generally  recognized. 

1  La  Presse  Med.,  1900,  p.  77. 

2  Fourth  Annual  Report  of  the  Cancer  Laboratory,  New  York  State  Board  of  Health, 
1902-1903,  p.  20. 

3  "  Verhandl.  d.  Komites  f.  Krebsforschung,"  S.  74,  Berlin,  1902. 

4  Lancet,  1904,  vol.  ii.,  p.  469  ;  also  ibid.,  1907,  vol.  ii.,  p.  358. 


THE  MICROBIC  THEORY  OF  CANCER  247 

In  a  recently  published  account  of  "  further  researches,"  the  authors 
claim  to  have  confirmed  their  previous  findings  ;  and  the  parasite  is  now 
identified  as  "  Spirochceta  microgyrata."  Thus  a  spirochaetan  origin  of 
cancer  is  suggested. 

As  Lubarsch  has  well  said,  those  who  claim  that  these  endocytes  are 
parasites,  must  not  only  prove  that  they  resemble  known  parasites  ; 
but  also  that  they  cannot  be  anything  else.  The  need  for  insisting  on  the 
strict  observance  of  this  wholesome  precaution  is  emphasized,  by  the 
recollection  of  the  innumerable  diverse  interpretations,  that  have  been 
placed  on  these  appearances  by  equally  competent  workers  ;  some  of 
•whom  (e.g.,  Plimmer  and  Sawtchenko)  have  even  regarded  the  very 
same  bodies  at  one  time  as  protozoa,  and  at  another  time  as  blasto- 
mycetes  etc. 

Very  thorough  investigations  as  to  the  nature  of  the  special  "  bird's- 
eye  "  cell  inclusions,  described  by  Soudakevitch,  Ruffer  and  Plimmer,  as 
typical  of  the  protozoan  cancer  parasite,  have  lately  been  made  by 
Greenough,1  Nosske,2  and  Honda.3  All  the  above  are  agreed  that  these 
endocytes  are  not  parasites  ;  but  secretory  products,  formed  in  cells  of 
glandular  origin — cancerous  as  well  as  non-cancerous  (e.g.,  chronic 
cystic  mastitis,  fibro-adenoma  etc.).  They  dispute  the  contention  of 
Plimmer  and  Gaylord,  that  inclusions  of  this  kind  are  met  with  in  all 
malignant  tumours,  having  found  them  absent  in  epidermoidal  cancer  of 
the  skin  and  in  sarcoma. 

Blum,4  the  latest  student  of  this  matter,  finds  no  reason  for  regarding 
these  bodies  as  parasites  ;  and  maintains  that  there  is  no  evidence  to 
connect  them,  in  any  way,  with  the  causation  of  cancer. 

Of  a  large  number  of  culture  experiments  made  in  various  media, 
with  cancerous  tissue,  0.  Richardson  5  was  unable  to  cultivate  from  the 
morbid  tissues  and  fluids,  any  specific  infecting  organism. 


General  Conclusions  as  to  Protozoa. 

Before  entering  on  any  discussion  as  to  the  setiological  significance 
of  the  hypothetical  protozoa  of  malignant  tumours,  we  want  to  be 
reasonably  assured  that  such  parasites  really  exist  in  these  tumours. 
Hence,  it  is  to  this  aspect  of  the  question,  that  we  must  first  of  all 
direct  our  attention. 

It  will  be  gathered  from  what  has  been  stated,  that  the  evidence 
hitherto  adduced  is  almost  entirely  histological ;  for,  the  results  of  so- 
called  cultures  and  of  inoculation  experiments,  in  this  connexion,  have 
established  nothing  definite. 

Even  if  pathologists  were  unanimous  in  interpreting  the  appearances 
revealed  on  microscopical  examination  of  malignant  tumours,  as  indica- 

1  Third  Report  of  the  Croft  Cancer  Commission  of   Harvard  Medical  School,  1905, 
p.  29. 

2  Deutsche  Ztits.  f.  Chir.,  1902,  Bd.  Ixiv.,  S.  352. 

3  Arch.  f.  path.  Anat.,  1903,  Bd.  clxxiv.,  S.  96. 

4  Ibid.,  1905,  Bd.  clxxix.,  S.  475. 

.  *  Second  Report  of  the  Croft  Cancer  Commission  of  Harvard  Medical  School,  1902, 
p.  46. 


248  THE  NATURAL  HISTORY  OF  CANCER 

tive  of  the  presence  of  protozoa  ;  in  the  absence  of  corroborative  evidence, 
such  unanimity  would  fall  far  short  of  scientific  proof.  But,  when  we  find 
that  most  pathologists  decisively  reject  this  interpretation,  maintaining 
that  the  bodies  which  have  been  thus  described  are  not  parasites  at  all, 
but  merely  products  of  the  biological  changes — often  degenerative — 
incidental  to  the  life  of  the  part,  secretory  products,  derivatives  of  the 
nuclei  or  protoplasm  of  the  tumour  cells,  of  leucocytes,  of  red  blood- 
globules  etc.  ;  the  futility  of  relying  on  the  appearances  revealed  by  the 
microscope,  for  the  proof  of  the  presence  of  parasitic  protozoa  in  malignant 
tumours,  becomes  apparent. 

It  is  passing  strange,  that  those  who  are  so  insistent  on  maintaining 
the  protozoan  nature  of  certain  appearances  revealed  by  the  histological 
examination  of  malignant  tumours  have,  with  singular  unanimity,  failed 
to  make  control  observations.  Had  they  done  so,  they  would  have  found 
similar  appearances  often  present  in  various  non-cancerous  conditions, 
e.g.,  in  chronic  cystic  mastitis,  in  mammary  adenoma  etc.  (Greenough)  ; 
in  variolous  and  vaccinal  lesions  (Pfeiffer,  Guarnieri,  Mann  etc.)  ;  in 
healing  wounds,  and  after  artificial  irritation  (Spirlas,  Pierallini,  D'Arcy 
Power,  Galeotti  etc.)  ;  in  syphilitic  lesions,  herpes,  endometritis,  mycosis 
fungoides  etc. 

Moreover,  in  undoubted  cases  of  human  psorospermosis,  such  as 
those  described  by  Leuckhart,  Albarran,  Keen,  Silcock,  Eve,  and  others, 
the  lesions  met  with  bore  no  resemblance  whatever  to  malignant  disease. 
Similarly  in  animals  (rabbits  etc.),  the  lesions  caused  by  these  parasites 
never  present  any  of  the  special  features  of  malignant  tumours. 

It  accords  with  this,  that  tumour  cells  containing  "  parasitic  protozoa" 
always  appear  to  be  in  a  state  of  degeneration  ;  and  to  be  incapable  of 
that  active  proliferation,  which  is  an  essential  feature  of  malignancy. 

Again,  the  chemical  reactions  of  malignant  tumours  are  very  different 
from  those  of  lesions  in  which  psorospermia  abound  ;  for,  they  contain 
neither  chitin,  cellulose,  nor  albumose  (Brodie,  Hewlett).  On  the  other 
hand,  they  are  rich  in  glycogen  ;  which,  according  to  Brault,  is  absent 
from  parasitic  pseudo-plasms.  Moreover,  "  falciform  bodies  "  have  never 
been  demonstrated  in  the  so-called  psorospermia  of  malignant  tumours  ; 
and  no  alkaloid  has  ever  been  separated  from  them. 

Before  such  bodies  as  those  described  by  Schaudinn,  Sjobring,  Max 
Schiiller,  Gaylord,  Feinberg,  Robertson  and  Wade,  can  be  accepted  as 
parasitic  protozoa,  the  possibility  of  their  being  derivatives  of  pre- 
existing somatic  structures  must  be  negatived. 

The  more  carefully  the  subject  is  considered,  the  clearer  it  appears  ; 
that  the  "  protozoon  of  cancer  "  has  failed  to  make  good  its  entity. 
This  hypothetical  microbe  appears  to  be  a  mere  figment  of  the  imagina- 
tion, which  has  been  projected  into  the  field  of  observation,  in  consequence 
of  errors  of  diagnosis  :  it  is  a  case  of  mistaken  identity. 

In  this  opinion,  modern  zoologists  are  at  one  with  pathologists  ;  thus 
Doflein,1  the  latest  investigator  of  the  protozoa,  says  :  "  The  zoologist 
cannot  at  present  admit,  that  any  one  of  the  so-called  cancer  parasites, 
is  a  protozoon." 

1   "Die  Protozoen  als  Parasiten  und  Krankheitserreger,"  Jena,  1901. 


THE  MICROBIC  THEORY  OF  CANCER  249 


Blastomycetes. 

The  third  great  movement  in  connexion  with  the  microbic  origin  of 
malignant  tumours  was  originated  by  Russell,1  who  (in  1890)  detected 
certain  "  fuchsin  bodies  "  in  cancerous  tumours,  which  he  regarded  as 
the  characteristic  organisms  of  cancer  ;  and  these  he  believed  to  be  para- 
sitic blastomycetes,  of  the  same  order  as  the  yeast  fungi.  It  cannot  be 
said  that  Russell's  views  met  with  much  support,  until  some  years 
later,  when  the  Italian  pathologists  took  the  matter  up  ;  and,  by  means 
of  experimental  methods,  aroused  fresh  interest  in  the  subject. 

It  is  especially  owing  to  the  work  of  Sanfelice,2  Director  of  the  Hygienic 
Institute  at  Cagliari  (Sardinia),  that  so  much  attention  has  centred  on 
the  blastomycetes  in  this  connexion.  Moreover,  he  removed  the  study 
of  the  subject  from  the  histological  to  the  experimental  region.  It 
appears  that,  even  as  early  as  1895,  he  was  engaged  in  studying  certain 
organisms  found  in  infusions  of  various  kinds  of  fruits  ;  and,  in  so  doing, 
he  was  struck  with  the  resemblance  which  some  of  them  presented  to 
the  so-called  "  fuchsin  "  bodies,  found  by  Russell  in  human  cancerous 
neoplasms.  Of  these  organisms  he  obtained  pure  cultures,  with  which 
he  proceeded  to  inoculate  the  tissues  and  organs  of  various  animals.  He 
thus  found  that  some  of  them  were  pathogenic,  the  effect  varying  in 
different  animals.  In  many  animals  nodular  swellings  were  produced 
at  the  seat  of  inoculation,  in  adjacent  lymph-glands,  and  sometimes  in 
more  distant  parts,  which  he  thought  might  not  unfairly  be  compared 
with  human  malignant  tumours. 

Sanfelice  had  no  doubt  that  the  organisms  he  experimented  with  were 
blastomycetes  ;  and,  the  pathogenic  form,  he  discriminated  as  Saccharo- 
•myces  neoformans.  In  most  cases,  the  tumours  thus  produced  were 
nothing  but  inflammatory  pseudo-plasms.  But,  with  cultures  of  a  microbe 
of  this  kind,  isolated  from  a  fermenting  infusion  of  lemon-skin,  he  claims 
to  have  produced,  by  inoculation,  malignant  epithelial  neoplasms 
(cancers)  in  dogs. 

When  these  cultures  were  injected  into  the  peritoneal  cavity,  nodular 
formations  at  first  resulted  ;  from  these  fresh  cultures  were  made,  and 
after  the  microbe  had  thus  been  passed  through  several  dogs,  it  was 
found  to  have  acquired  increased  virulence. 

Of  thirty  dogs  inoculated  with  cultures  thus  produced,  in  two  Sanfelice 
claims  to  have  caused  true  epithelial  cancer. 

In  the  case  of  a  bitch  inoculated  in  the  posterior  mammary  region, 
there  was  considerable  tumefaction  at  the  seat  of  inoculation  one  month 
afterwards.  The  animal  then  became  cachectic,  and  died  ten  months 
after  inoculation.  Besides  the  mammary  tumour,  post-mortem  examina- 
tion revealed  enlargements  of  the  adjacent  inguinal  and  abdominal 
lymph-glands.  Histologically  examined,  all  of  these  tumours  showed 

1  British  Medical  Journal,  1892,  vol.  ii.,  p.  1356. 

2  Cent.  f.  Bakt.,  etc.,  1895,  Bd.  xvii.,  S.  113  and  625;  Bd.  xviii.,  S.  521;  Bd.  xxiii., 
SS.  155  and  276 ;  and  Bd.  xxi.,  1902,  S.  254.     Also  series  of  articles  in  Zeits.  f.  Hygiene 
und  Infections-krankheiten,  1895,  Bd.   xxi.,  SS.  32  and  394  ;   Bd.  xxii.,  1896,  S.  171  ; 
Bd.  xxvi.,  S.  298  ;  Bd.  xxix.,  1898,  S.  463. 


250  THE  NATURAL  HISTORY  OF  CANCER 

the  structure  of  glandular  cancer.  Numerous  "  parasites  "  were  present 
in  them,  but  no  cultures  could  be  obtained.  The  latter  defect  is  unfortu- 
nate, as  the  possibility  of  the  animal  having  been  previously  affected 
with  mammary  cancer,  to  which  bitches  are  exceedingly  prone,  thus 
cannot  be  excluded. 

A  similar  defect  characterizes  the  other  positive  result ;  when,  after 
inoculation  of  the  testes,  a  secondary  tumour  formed  in  the  penis. 
Sanfelice  also  claims  to  have  isolated  blastomycetes  from  human 
malignant  tumours  ;  but,  when  cultures  of  these  organisms  were  injected 
into  various  animals,  no  tumour  formation  ensued. 

In  a  recent  publication  x  Sanfelice  still  claims,  that  he  can  produce 
malignant  tumours  in  animals,  by  inoculating  them  with  blastomycetes 
and  their  soluble  products. 

Roncali,2  investigating  the  subject  chiefly  from  the  histological  stand- 
point, has  detected  in  human  cancers  and  sarcomas  intra-  and  extra- 
cellular bodies,  similar  to  those  described  by  Sanfelice.  He  is  convinced 
that  these  bodies  are  parasitic  blastomycetes. 

With  Sanfelice,  in  1898,  he  succeeded  in  isolating  similar  organisms 
from  human  cancerous  tumours,  which  they  found  to  have  pathogenic 
properties  ;  but,  when  these  were  injected  into  certain  animals,  only 
pseudo-inflammatory,  tumour-like  swellings  resulted.  These  cultures 
were  made  with  difficulty,  and  they  soon  lost  their  virulence,  so  that 
nothing  further  was  accomplished  in  this  direction. 

At  the  meeting  of  the  Italian  Surgical  Congress,  in  1900,  Roncali 
again  took  up  this  question.  He  described  the  appearances  found  on 
histological  examination,  of  an  intra-cranial  fibre-sarcoma  of  the  dura 
mater.  This  tumour  teemed  with  parasitic  blastomycetes.  After 
having  fully  described  their  morphological  features  and  their  precise 
localization  in  the  tumour,  which  were  such  as  clearly  indicated  genetic" 
correlation,  he  arrived  at  the  following  conclusions  : — (1)  This  case  proved 
that  blastomycetes  could  not  be  mere  accidental  epiphytes  in  malignant 
tumours.  (2)  Although  he  failed  to  isolate  and  cultivate  blastomycetes 
from  the  tumour,  this  was  no  proof  that  they  did  not  exist,  nor  did  it 
imply  that  they  were  products  of  degeneration  ;  for,  as  Sanfelice  had 
shown,  when  the  parasites  assumed  the  form  of  "  Russell's  bodies," 
they  were  no  longer  cultivable.  (3)  Provided  one  knew  how  to  recog- 
nize them,  and  had  the  patience  to  search  for  them,  these  parasites  could 
always  be  found  in  malignant  tumours.  (4)  The  so-called  parasitic 
protozoa  and  coccidia,  described  by  other  investigators  as  being  con- 
stantly present  in  malignant  tumours,  were  nothing  but  blastomycetes, 
as  the  author  has  maintained  ever  since  1895.  (5)  Blastomycetes  were 
the  real  setiological  factor  of  malignant  tumours  (epithelioma  and  sar- 
coma), as  Sanfelice  had  experimentally  demonstrated. 

In  the  interesting  discussion  which  followed  the  reading  of  Roncali's 
paper,  Bastianelli  maintained  that  it  was  not  sufficient  to  have  stained 
and  described  these  bodies,  to  prove  that  they  were  blastomycetes.  It 

1  Annali  d'igiene  sperimentali,  1907,  vol.  xvii. 

2  II  Policlinico,  October  1,  1895;  and  ibid.,  October  31,  1896  (suppl.):  also  Cent.  f. 
Bakt.,  etc.,  1895,  Bd.  xviii.,  Heft  12-15  ;  ibid.,  1898,  Bd.  xxiv.,  Abth.  i.,  S.  61. 


THE  MICROBIC  THEORY  OF  CANCER  251 

was  necessary  to  give  this  proof,  which  the  author  had  not  done.  Biondi 
said  that  of  all  the  researches  hitherto  made  in  connexion  with  the  para- 
sitic origin  of  malignant  tumours,  the  only  really  important  facts  hitherto 
obtained,  were  the  two  positive  results  announced  by  Sanfelice  ;  and  these 
undoubtedly  gave  food  for  thought. 

Durante  could  not  support  the  blastomycetic  theory  of  the  origin  of 
malignant  tumours,  because  the  precise  conditions  which  would  enable 
him  to  say  that  the  blastomycetes  were  really  the  causal  factor  were 
wanting.  Sanfelice's  experiments  were  lacking  in  this  respect.  He  had 
seen  his  specimens  ;  but  was  not  convinced  as  to  the  epithelial  nature  of 
the  experimentally  produced  tumours. 

Maffuci  and  Sirleo,1  as  the  result  of  numerous  inoculation  experi- 
ments on  various  animals,  and  of  many  culture  tentatives  with  human 
malignant  tumours,  sum  up  their  conclusions  as  follows  :  (1)  On  a  priori 
grounds,  the  infective  origin  of  malignant  tumours  is  probable.  (2)  The 
infective  agent  has  not  yet  been  determined,  by  either  histological  or 
experimental  researches.  (3)  Investigations  relating  to  the  infective 
agents  of  tumours,  should  not  be  limited  to  one  class  of  parasites. 
(4)  Among  the  blastomycetes,  some  have  pathogenic  properties.  (5)  The 
lesions  induced  by  blastomycetes,  are  quite  different  from  such  new 
growths  as  carcinoma  and  sarcoma.  (6)  Pathogenic  blastomycetes  may 
induce  septicaemia,  suppuration,  and  chronic  inflammatory  changes  of 
granulomatous  nature.  (7)  Blastomycetes  found  in  human  malignant 
tumours,  when  inoculated  into  animals,  have  hitherto  producd  only 
ordinary  inflammatory  pseudo-plasms.  The  authors  deny  that  malignant 
epithelial  tumours  can  be  produced  in  dogs,  by  pure  cultures  of  blasto- 
mycetes, as  Sanfelice  alleges.  (8)  In  human  cancerous  and  sarcomatous 
tumours  blastomycetes  cannot  always  be  demonstrated,  either  histo- 
logically  or  by  culture.  (9)  In  ulcerating  human  malignant  tumours, 
blastomycetes  may  be  found.  (10)  The  conditions  under  which  this 
happens,  and  the  distribution  of  the  blastomycetes,  are  such  as  lead  to 
the  inference  that  the  infection  has  been  superadded.  (11)  While  not 
denying  the  possibility  that  blastomycetes  may  cause  malignant  tumours, 
the  authors  maintain  that  this  has  not  been  proved  experimentally.  The 
tumour-like  swellings  produced  in  animals,  by  inoculation  with  pure 
cultures  of  blastomycetes,  are  inflammatory  pseudo-plasms  (granulo- 
mata),  and  never  true  malignant  tumours. 

Corselli  and  Frisco  2  isolated  and  obtained  pure  cultures  of  blasto 
mycetes,  from  a  sarcomatous  tumour  of  the  mesenteric  glands  of  man 
With  these  cultures  they  inoculated  guinea-pigs,  rabbits,  and  dogs ; 
and  in  several  of  the  animals  thus  experimented  on,  they  claim  to  have 
produced  similar  sarcomatous  growths. 

Even  before  the  Italian  pathologists  took  the  matter  up,  several  well- 
marked  instances  of  blastomycetic  infection  in  humanity  had  been 
reported. 

1  Arch,  ed  atti.  d.  Soc.  Ital.  di  Chir.,  Roma,  1897,  vol.  xi.,  p.  Ixvii. ;  also  Cent.  f.  Path, 
u.  path.  Anat.,  1895,  Bd.  iv.,  S.  305  ;  Bd.  vi.,  S.  438  ;  also  Zeits.  /.  Hygieneu.  Infections- 
krankheiten,  1898.  Bd.  xxvii.,  S.  438  ;  and  II  Policlinco,  vol.  v.,  May,  1895. 

2  Cent.  f.  Bakt.,  etc.,  1895,  Bd.  xviii.,  Heft  12  and  13. 


252  THE  NATURAL  HISTORY  OF  CANCER 

Thus,  Busse,1  in  1894,  published  the  case  of  a  woman,  aged  thirty-one, 
with  a  suppurating  pseudo-sarcomatous  tumour  of  the  tibia,  of  slow 
growth  ;  in  which  he  found,  in  the  primary  as  well  as  in  the  secondary 
swellings,  numerous  blastomycetes,  as  determined  histologically  and  by 
experimental  inoculation  of  animals  therewith.  Pure  cultures  of  these 
were  also  made  ;  and  when  rabbits,  dogs,  rats  etc.,  were  inoculated  with 
them,  suppurative  local  swellings  resulted.  In  white  mice  these  inocula- 
tions caused  death,  and  the  fungi  were  demonstrated  in  the  animals' 
blood.  Intra-peritoneal  inoculation  of  rats,  resulted  in  the  production 
of  enormous  tumours,  which  often  generalized. 

The  patient  above  referred  to,  who  presented  other  signs  of  general 
blastomycetic  infection,  died  thus  thirteen  months  after  softening  of  the 
tibial  tumour,  in  a  state  of  extreme  marasmus.  Besides  the  tibial 
tumour,  similar  swellings  had  formed  over  the  sixth  left  rib  and  over 
the  right  ulna.  At  the  necropsy,  there  was  general  enlargement  of  the 
lymph-glands,  besides  softening  nodules  in  the  spleen,  kidney  and  lung. 
Histologically  examined,  all  of  these  lesions  teemed  with  blastomycetes,  of 
which  cultures  were  made,  which  succeeded  best  on  potato.  Besides  these 
microbes,  the  tumour-like  swellings  comprised  numerous  giant-cells,  and 
much  immature  connective  tissue,  with  pus-cells  etc. 

Kahane  2  also  demonstrated  and  made  pure  cultures  of  blastomycetes, 
from  cancers  of  the  uterus  etc.  ;  and,  in  some  cases  of  this  kind,  he  claims 
to  have  seen  similar  parasites  in  the  blood. 

Curtis3  of  Lille  has  recorded  the  history  of  a  soldier,  with  a  large, 
soft,  pseudo-myxomatous  tumour  in  the  upper  part  of  the  thigh,  which 
clinically  resembled  sarcoma.  There  was  another  similar  tumour  in 
the  lumbar  region.  These  tumours  were  situated  in  the  subcutaneous 
tissue.  When  laid  open,  the  groin  tumour  looked  like  myxo-sarcoma. 
Histologically  examined,  large  parts  of  it  were  comprised  almost  entirely 
of  masses  of  blastomycetes — extra-  and  intra-cellular — supported  by  a 
vascular  connective-tissue  network.  The  tumour  substance  had  con- 
tagious properties  ;  for,  a  fragment  of  it  implanted  into  a  rabbit — in  the 
course  of  ten  days — gave  rise  to  a  tumour,  the  size  of  a  small  orange, 
which  also  teemed  with  yeast-like  fungi.  The  organism  grew  rapidly 
on  potato  and  gelatin,  multiplying  by  gemmation  ;  and  it  is  named  by 
the  author  Megalococcus  myxoides.  The  injection  of  pure  cultures  into 
white  rats  and  mice,  caused  tumours — like  those  in  the  soldier — to  form 
at  the  seat,  of  inoculation,  with  metastases  in  internal  organs  etc. 

These  experiments  by  Busse  and  Curtis,  taken  in  conjunction  with 
those  by  Sanfelice  and  his  followers,  show  that  for  mankind  and  animals, 
certain  yeasts  may  give  rise  to  quasi-malignant  pseudo-plasms. 

Monsarrat 4  claims  to  have  isolated  an  organism  from  cancer,  grown 
in  various  media,  and  to  have  inoculated  animals  with  pure  cultures  of 
it,  causing  in  them  endotheliomatous  new  growths,  whence  the  parasites 

1  Cent.  f.  Eakt.,  etc.,  1894,  Bd.  xvi.,  S.  175  ;  also  Arch.  f.  path.  Anat.,  1895,  Bd.  cxl., 
S.  23;  and  ibid.,  1896,  Bd.  cxliv.,  S.  360. 

2  Cent.  f.  Bakt.,  1894,  Bd.  xv.,  S.  629  ;  and  Bd.  xviii.,  S.  616. 

3  Ann.  de  I'Inst.  Pasteur,  1896,  t.  x.,  p.  448. 

4  Proceedings  of  the  Royal  Society,  1900,  vol.  Ixvi.,  p.   58;   also    Liverpool  Med.- 
Chir.    Journal,   1900,  vol.  xx.,  p.  318  ;   and  Transactions  of  the   Pathological  Society, 
London,  1905,  vol.  Ivi.,  p.  272. 


THE  MICROBIC  THEORY  OF  CANCER  253 

were  recovered.  These  bodies  were  identical  with  the  blastomycetes 
described  by  Sanfelice.  Cultures  were  difficult  to  obtain  ;  for,  of  twenty- 
seven  mammary  cancers  systematically  examined,  only  one  yielded  a 
positive  result.  The  organism  grew  but  slowly  on  ordinary  media.  In 
six  cases  he  examined  the  blood  of  patients  with  advanced  cancer,  but 
in  all  the  results  were  negative.  Monsarrat's  cultures  soon  lost  their 
virulence,  and  became  inert.  Attempts  to  sustain  or  increase  their 
pathogenic  properties,  by  successive  passage  through  guinea-pigs  and 
other  animals,  were  unsuccessful.  In  his  latest  publication  (1905), 
Monsarrat  maintains  that  this  organism  is  the  specific  cause  of  mammary 
cancer,  and  by  injecting  it  into  guinea-pigs  and  dogs,  he  claims  to  have 
caused  cancerous  tumours  in  them  ;  but,  a  committee  of  the  London 
Pathological  Society  having  examined  his  specimens,  found  in  them 
"  nothing  suggestive  of  carcinoma." 

Leopold  l  found  blastomycetes  in  non-ulcerated  cancers  from  different 
parts  of  the  body.  Of  twenty  such  tumours  examined,  he  obtained 
cultures  from  four.  His  best  material  was  derived  from  ovarian  cancers. 
A  special  feature  of  his  work  is  the  prolonged  study  he  made  of  particles 
of  cancer  substance  in  hanging  drops  of  sterile  bouillon,  in  a  specially 
constructed  thermostatic  microscope.  In  these  preparations,  some  of 
which  were  preserved  for  200  days  or  more,  blastomycetes  were  seen  in 
various  stages  of  development ;  and  their  multiplication  by  budding 
was  studied.  The  organisms  isolated  from  all  of  these  four  cancers, 
caused  glucose  to  undergo  alcoholic  fermentation.  In  fixed  preparations, 
double-contoured  and  budding  organisms,  as  well  as  round  bodies,  were 
found  ;  and  there  could  be  no  doubt  as  to  their  being  blastomycetes. 

The  following  experiments  on  animals  were  made  : — (1)  A  small 
piece  of  fresh  human  cancer  was  implanted  into  the  abdomen  of  a  rabbit, 
with  aseptic  precautions  :  on  the  death  of  the  animal,  four  years  and  five 
months  afterwards,  there  was  found  a  suppurating  tumour  in  the  abdo- 
men and  epithelial  overgrowths  in  the  lung.  (2)  Fresh  cancer  substance 
implanted  in  the  abdomen  of  a  rat  was  followed  by  death,  with  the  pro- 
duction of  "  adeno-sarcoma  "  in  the  right  groin.  (3)  A  pure  culture  from 
cancer  of  the  human  ovary,  injected  into  the  testis  of  a  white  rat,  caused 
the  formation  of  a  sarcomatous  tumour  at  the  seat  of  inoculation  and  of 
multiple  sarcomata  (myeloid  and  round-celled)  in  the  abdomen. 

In  the  material  injected,  blastomycetes  were  present ;  similar  organisms 
were  found  in  the  experimentally  produced  tumours,  from  which  pure 
cultures  were  again  secured. 

A  curious  feature  of  these  experiments  was  the  production  of  sarcoma 
in  animals,  with  organisms  derived  from  human  carcinomata. 

Of  fifteen  human  malignant  tumours  removed  with  the  strictest 
aseptic  precautions,  and  examined  for  blastomycetes,  Carini 2  got  only 
one  successful  culture.  This,  he  thought,  was  probably  a  contamination 
product.  He  never  succeeded  in  producing  a  malignant  tumour,  by  the 
injection  of  pure  cultures  into  animals.  Histological  examination  of 
forty-four  human  tumours  (mostly  malignant),  showed  the  presence  of 
"  Russell's  bodies  "  in  eighteen.  Similar  bodies  were  found  in  non- 
1  Arch.  f.  Gyndkologie,  1900,  Bd.  Ixi.,  S.  77.  2  II  Policlinico,  AprU  15,  1900. 


254  THE  NATURAL  HISTORY  OF  CANCER 

malignant  tumours,  and  even  in  normal  structures,  such  as  the  prostate. 
He  considered  that  the  staining  reactions  of  these  bodies  were  not  really 
characteristic  of  blastomycetes. 

Petersen  and  Exner,1  experimenting  on  animals  with  Sanfelice's 
Saccharomyces  neoformans  and  other  blastomycetes,  found  that  the 
cultures  produced  large  nodules  at  the  seat  of  inoculation,  with  secondary 
formations  in  the  kidney,  spleen,  lungs  and  lymph-glands.  None  of  these 
formations  presented  the  structure  of  human  cancer  or  sarcoma — they 
were  rather  granulomata,  comprising  many  giant-cells  and  masses  of  the 
parasites.  From  the  histological  examination  of  many  specimens,  they 
concluded  that  the  endocytes  of  human  malignant  tumours  are  very  rarely 
due  to  parasites. 

Cultures  of  yeasts  from  malignant  tumours  so  seldom  occur,  that  the 
few  successful  results  may  be  ascribed  to  accidental  contamination. 
Those  animal  and  human  diseases  that  have  been  recognized  with  cer- 
tainty, as  due  to  yeast  infection  (cutaneous  ulcers,  inflammatory  swellings, 
endometritis,  abscesses  etc.),  have  no  resemblance  whatever  to  cancer. 
The  tumour-like  lesions  produced  by  yeast  inoculations  are  granulomata, 
and  not  true  tumours. 

Wlaeff  and  Weinberg2  repeated  Sanfelice's  inoculation  experiments, 
but  failed  to  produce  any  tumour  having  the  least  resemblance  to  cancer 
or  sarcoma.  As  a  rule,  only  granulomatous  swellings  resulted  ;  but,  in 
a  few  cases,  pseud-adenomatous,  cyst-like,  and  papilliferous,  formations 
followed.  Wlaeff  was  able  to  exalt  the  virulence  of  pathogenic  blasto- 
mycetes, by  repeated  passage  through  animals.  Cultures  thus  treated 
produced  different  results  when  inoculated  into  various  animals  ;  in 
some  they  caused  septicaemia,  in  others  local  swellings  and  cysts,  and  in 
guinea-pigs  a  cutaneous  lesion  like  lupus  vulgaris.  Weinberg  found  that 
the  cysts  produced  by  injection  of  feebly  virulent  cultures,  contained 
numerous  more  or  less  degenerate  blastomycetes,  the  cyst  wall  being  of 
inflammatory  origin.  Wlaeff  isolated  blastomycetes  from  the  juice  of 
a  sarcoma  of  the  human  uterus,  and  obtained  pure  cultures  of  them.  He 
also  demonstrated  their  presence  histologically  in  the  tumour. 

In  subsequent  publications,  Wlaeff  3  concluded  that,  since  numerous 
investigators  have  isolated  blastomycetes  in  pure  cultures  from  malignant 
tumours,  and  have  by  inoculation  with  these  produced  infective  growths 
in  animals,  these  organisms  are  the  causative  agents  of  malignant  disease. 
For  various  non-malignant  tumours  (adenoma,  fibroma,  cysts  etc.),  he 
advocates  a  similar  aetiology. 

He  prepared  a  serum  for  inoculating  animals  against  malignant 
disease,  and  found  that  in  rats  and  monkeys,  it  conferred  protection 
against  growths  caused  by  blastomycetes.  Wlaeff  subsequently  used 
this  serum,  for  the  treatment  of  sixty  cases  of  human  malignant  tumours  ; 
and  came  to  the  conclusion,  that,  when  it  was  injected  early,  before 
lymph-gland  dissemination  had  supervened,  it  had  a  curative  effect. 

1  Beitrage  z.  klin.  Chir.,  1899,  Bd.  xxv.,  S.  769. 

3  Butt,  et  mem.  de  la  Soc.  Anat.  de  Paris,  t.  Ixxiv.,  1899,  pp.  706  and  842;  also  ibid., 
t.  Ixxv.,  1900,  p.  147  ;  also  C.  JR.  Soc.  de  Biologie,  1900,  lii.,  p.  759. 

3  La  Presse  Med.,  1901,  p.  145;  and  Eev.  d'Obstet.  et  de  Gyn.,  1904,  No.  8,  p.  164; 
also  C.  R.  Soc.  de  Biologie,  1900,  lii.,  p.  1030  ;  ibid.,  1901,  liii.,  pp.  106  and  285. 


THE  MICROBIC  THEORY  OF  CANCER  255 

The  serum  employed  was  obtained  from  the  blood  of  asses  and  geese, 
that  had  previously  undergone  a  series  of  inoculations  with  blastomycetic 
cultures. 

Foulerton  *  has  made  inoculation  experiments  in  animals  with  various 
pathogenic  yeasts.  In  most  cases  these  caused  death  in  from  a  few  days 
to  a  few  weeks.  In  many  instances  granulomatous  swellings  formed  at 
the  site  of  inoculation  ;  and  from  these  the  yeasts  were  again  cultivated. 
He  concludes  that  :  "  Considerably  more  evidence  than  is  now  available 
must  be  brought  forward,  before  we  can  form  any  opinion  as  to  whether 
Russell's  fuchsin  bodies  etc.,  are  merely  parts  of  the  cancer  cells  them- 
selves, or  whether  they  are  of  the  nature  of  animal  or  vegetable  parasites." 
It  is  not  improbable  that  some  tumours,  now  classed  as  sarcomata,  may 
really  be  due  to  yeast  infection  ;  but,  "  as  to  the  exact  causation  of  carci- 
noma we  are  still  absolutely  ignorant." 

Klein,2  having  discovered  a  pathogenic  yeast  in  some  ordinary 
country  milk,  found  that  when  inoculated  subcutaneously  into  guinea- 
pigs,  it  produced  tumour-like  swellings  at  the  seat  of  inoculation.  When 
the  animals  were  killed  some  weeks  later,  the  tumours  were  found  to  be 
crowded  with  yeast-ceUs.  Other  guinea-pigs  were  inoculated  with  the 
juice  of  these  tumours  and  with  sub-cultures,  with  the  result  that  similar 
tumours  again  formed,  and  death  sometimes  resulted.  In  the  latter 
cases,  yeast-cells  were  found  in  the  blood.  This  yeast  seemed  to  belong 
to  the  same  group  as  the  blastomycetes  of  Sanfelice. 

Gilchrist3  has  described  a  case  of  skin  disease  ("blastomycetic 
dermatitis  ")  in  man,  in  which  the  lesion  teemed  with  blastomycetes, 
wliich  were  seen  multiplying  by  budding.  He  considers  that  most  of 
the  so-called  parasites,  in  certain  skin  affections,  are  merely  products 
of  nuclear  and  protoplasmic  changes  of  epithelial  cells,  and  not  organisms. 
Since  formations  of  this  kind  are  found  in  simple  skin  diseases,  as  well  as 
in  cancers,  they  can  have  no  specific  causal  relation  to  malignancy. 
Clinically  the  above  case  resembled  "  scrofuloderma." 

Gilchrist  and  Stokes  4  have  since  reported  another  example  of  human 
blastomycetic  infection.  In  this  case  the  patient  was  a  man,  aged 
thirty-three,  with  a  cutaneous  disease  like  lupus  vulgaris.  It  began 
eleven  and  one-half  years  previously,  as  a  pustular  pimple  on  the  back 
of  his  left  ear.  Thence  the  morbid  process  spread  slowly  over  the  face, 
the  older  parts  cicatrizing.  A  similar  lesion  formed,  soon  after  the 
initial  outbreak,  on  the  back  of  his  hand  ;  but  this  healed,  on  treatment 
with  caustic,  about  four  years  after  its  first  appearance.  Six  months 
later  a  third  lesion  appeared  on  the  scrotum,  which  spread  for  a  year, 
and  then  healed  spontaneously.  Other  lesions  formed  on  the  left  thigh, 
back  of  the  neck  etc.,  and  likewise  healed  spontaneously  after  some 
time.  There  was  no  enlargement  of  the  adjacent  lymph-glands,  and  the 
patient's  health  remained  good.  There  was  no  history  of  tubercle]  or 
syphilis. 

1  Journal  of  Pathology  and  Bacteriology,  May,  1899,  p.  57 ;  also  ibid.,  1900,  vol.  vi.,  p.  154. 

2  Transactions  of  the  Pathological  Society,  London,  1901,  vol.  lii.,  p.  270. 

3  Johns  Hopkins  Hospital  Reports,  1896,  vol.  i.,  p.  269. 

4  Journal  of  Experimental  Medicine,  January,  1898,  vol.  iii.  ;  also  Butt.  Johns  Hopkins 
Hospital,  July,  1896. 


256  THE  NATURAL  HISTORY  OF  CANCER 

Sections  of  the  cutaneous  lesions,  on  microscopical  examination, 
showed  numerous  budding  blastomycetes,  in  association  with  which  were 
many  almost  typical  tubercles.  The  organisms  were  mostly  extra- 
cellular, comparatively  few  being  included  in  the  giant-cells.  Pure 
cultures  were  obtained  from  the  lesion,  which  grew  well  on  potato  and 
beer- wort  agar.  The  cultures  showed  both  budding  forms  and  mycelium, 
although  the  latter  was  not  met  with  in  the  lesion.  A  horse,  a  sheep, 
dogs  and  guinea-pigs  were  successfully  inoculated,  nodules  forming 
which  resembled  tumours,  especially  in  the  lungs.  Since  the  parasite 
did  not  ferment  sugar,  and  produced  mycelium  in  cultures,  it  might 
belong  to  the  blastomycetes  or  o'idia.  The  authors  suggest  that  all 
quasi-tuberculous  lesions  of  the  skin  should  be  examined  for  similar 
organisms,  which  can  easily  be  done  by  soaking  unstained  sections  in 
liquor  potassae,  when  the  organisms  may  be  recognized  under  the  micro- 
scope as  doubly  contoured  refractive  bodies. 

A  considerable  number  of  somewhat  similar  cases  have  since  been 
recorded,  in  some  of  which  the  lesions  were  very  like  those  of  ulcerated 
cutaneous  cancer. 

Owens,  Eisendrath,  and  Ready1  have  described  an  instance  of  this  kind. 

Hyde,  Hektoen,  and  Bevan  2  have  reported  the  case  of  a  man,  aged 
fifty-six,  with  a  peculiar  form  of  skin  disease  caused  by  blastomycetes.  It 
began  four  years  previously,  as  a  raised  red  tubercle  which  gradually 
extended  ;  until,  when  it  had  attained  considerable  size,  it  was  removed 
by  operation.  A  warty  growth  then  appeared  on  his  hand.  A  year  later 
this  was  extirpated,  and  examined  by  Hektoen.  Sections  under  the 
microscope  showed  blastomycetes  ;  and,  in  cultures,  mycelium  appeared. 
Rats  and  mice  subcutaneously  inoculated  died  in  a  few  days  ;  and  similar 
organisms  were  found  in  the  lesions  as  in  the  inoculation  sites.  A  striking 
feature  of  the  histological  sections  was,  the  epidermoidal  hyperplasia  and 
its  branching  ingrowths.  In  the  vicinity  were  numerous  small  aggrega- 
tions of  leucocytes  and  miliary  abscesses,  and  in  these  localities  giant- 
cells  were  plentiful. 

The  numerous  publications  on  this  subject,  have  been  ably  reviewed 
and  summed  up  in  Ricketts'  3  interesting  monograph,  to  which  the  reader 
is  referred  for  further  details  as  to  the  cases  etc.  He  noticed  that,  in 
several  instances,  the  cutaneous  lesions  were  "  carcinomatoid  "  in  their 
gross,  and  even  to  some  extent  in  their  minute  structural  features  ; 
while  still  more  cases  simulated  skin  tuberculosis.  Histologically  the 
lesions  comprised  hyperplasia  of  the  deeper  layers  of  the  epidermis,  with 
ingrowing  processes  of  the  same,  and  infiltration  of  all  the  constituents 
of  the  cutis  by  leucocytes,  with  minute  abscesses  in  the  corium  etc.  The 
microbes  producing  these  lesions  comprised  three  types — oidium-like 
(torula),  blastomycetoid  (saccharomycetes  or  yeasts),  and  hyphomycetoid 
(mould  fungi),  most  of  the  organisms  appertaining  to  the  first-named 
group. 

In  addition  to  these  skin  lesions,  in  several  recorded  cases,  the  malady 

1  "  Pseudo-epithelioma  with  Blastomycetes,"  Annals  of  Surgery,  1899,  vol.  xxx.,  p.  545. 

2  British  Journal  of  Dermatology,  1898,  vol.  ii.,  No.  129. 

3  Journal  of  Medical  Research,  February,  1902  ;  and  December,  1901,  p.  377. 


THE  MICROBIC  THEORY  OF  CANCER  257 

presented  in  mankind  as  a  generalized  infection,  with  fatal  issue  in  a  few. 
Cultures  were  obtained  from  the  pus,  and  from  the  diseased  tissues. 
Attempts  to  produce  the  typical  lesions  in  mankind,  by  inoculation  with 
cultures,  have  so  far  failed — most  individuals  being  naturally  immune  ; 
animal  inoculation  has  also  generally  been  unsuccessful,  but  in  a  few 
cases  tumour-like  nodules  formed,  and  oftener  abscesses. 

Foulerton1  has  published  the  results  of  further  study  of  this  matter, 
comprising  the  bacteriological  examination  of  several  hundred  human 
malignant  tumours.  In  the  course  of  this  research,  various  types  of 
microbes  were  cultivated  from  many  of  the  tumours  examined  ;  but,  in 
not  a  single  specimen,  was  a  yeast  found.  Hence,  he  regards  the  presence 
of  yeasts  in  such  cultures  as  the  result  of  contamination  ab  extra  ;  and, 
the  cultures  actually  obtained,  he  considers  as  due  to  aerial  contamina- 
tion, terminal  infection,  or  invasion  from  an  ulcerated  surface.  His 
general  conclusions  are  as  follows  : — A  hypothetical  cancer  parasite  does 
not  in  any  way  elucidate  the  pathology  of  cancer.  So  far  as  theoretical 
considerations  go,  the  probabilities  are  against  the  theory  of  cancer  being 
a  parasitic  disease.  There  is  no  evidence  that  any  of  the  parasites  which 
have  been  described  as  the  cause  of  cancer,  have  any  setiological  relation 
to  the  disease. 

Nichols,2  as  the  result  of  a  thorough  study  of  the  subject,  has  inde- 
pendently arrived  at  very  similar  conclusions,  which  he  formulates  as 
follows  : — 

Certain  blastomycetes  can  live  and  multiply  in  human  and  animal 
tissues,  producing  local  lesions,  and  disseminating  in  distant  parts,  i.e., 
they  are  pathogenic.  These  lesions  are  never  really  cancerous.  Blasto- 
mycetic  infection  is  rare  in  humanity.  Blastomycetes,  as  a  rule,  cause 
marked  tissue  proliferation,  with  but  little  infiltration  by  leucocytes,  i.e., 
their  toxic  power  is  small.  The  morphology  of  the  so-called  "  cancer 
bodies,"  is  not  identical  with  that  of  the  blastomycetes.  Blastomycetes 
are  not  constantly  present  in  human  malignant  tumours.  Even  if  blasto- 
mycetes do  occur  in  human  cancers,  they  are  never  found  in  such  relation 
to  the  morbid  formation,  as  to  justify  the  belief  that  they  are  the  cause 
of  the  disease.  A  general  survey  of  the  ascertained  facts,  reveals  no 
evidence  of  any  weight,  that  blastomycetes  have  anything  to  do  with  the 
causation  of  human  cancers. 

Since  Koch  formulated  his  celebrated  postulates,  for  determining  the 
setiological  relation  of  a  parasite  to  a  given  morbid  condition,  an  addi- 
tional test  has  been  established  by  the  study  of  agglutinative  reactions. 
In  this  connexion,  Malvey3  has  shown  that  the  serum  of  animals  inoculated 
with  yeasts,  has  the  power  of  agglutinating  those  yeasts.  Tested  in  this 
way,  the  "  cancer  yeasts  "  fail  to  give  any  indications  suggestive  of  casual 
relationship  to  cancer  ;  for,  as  Brauha  4  has  proved,  the  serum  of  cancer 
patients  when  thus  tested,  does  not  give  the  agglutin  reaction. 

Skchiwan,5   recognizing   the   existence   of   blastomycetes   in   animal 

1  Practitioner,  1902,  vol.  Ixix.,  p.  213;  and  Middlesex  Hospital  Cancer  Reports,  1902, 
vol.^i. 

2  Second  Report  of  the  Cancer  Committee  of  Harvard  Medical  School,  1902,  p.  80. 

3  Cent.  f.  Bakt.,  etc.,  1901,  Bd.  xxix..  S.  688. 

4  Ibid.,  Ed.  xxx.,  S.  945.  5  Ann.  de  I'Inst.  Pasteur,  1899,  t.  xiii.,  p.  771. 

17 


258  THE  NATURAL  HISTORY  OF  CANCER 

bodies,  has  proceeded  to  study  their  fate  under  these  circumstances. 
Working  with  Saccharomyces  subcutaneus  tumefaciens  of  Curtis,  and 
other  yeasts,  he  concluded  that  the  destruction  of  pathogenic  as  well  as 
of  non-pathogenic  blastomycetes,  is  effected  by  the  digestive  powers  of 
leucocytes,  which  take  up  the  living  organisms  and  destroy  them  (phago- 
cytosis). Skchiwan  claims  to  have  seen  yeasts  multiply  by  budding 
within  the  phagocytes.  He  concludes  that  the  destruction  of  yeasts 
within  the  body  takes  place,  in  accordance  with  the  general  laws  of 
phagocytosis.  The  capsule,  which  sometimes  forms  round  blasto- 
mycetes embedded  in  the  tissues,  he  regards  as  a  defensive  arrangement 
by  the  organism  against  the  further  spread  of  the  parasites. 

In  concluding  this  section  on  the  blastomycetes  and  their  supposed 
>•  relation  to  tumour  formation,  attention  ought  to  be  called  to  De  Backer's1 
work  in  this  direction.  De  Backer  approached  the  subject  from  a  totally 
different  standpoint  to  that  adopted,  by  any  of  those  to  whose  work  I 
have  previously  referred.  He  thought  that  by  the  introduction  of  blasto- 
mycetes into  the  body,  an  artificial  phagocytosis  might  be  set  up,  by 
which  any  pathogenic  microbes  that  were  present  would  be  "Destroyed. 
Assuming  that  cancer  was  a  germ  disease,  he  proposed  to  treat  it  and 
other  germ  diseases  such  as  tuberculosis,  diphtheria,  typhoid  fever  etc., 
by  the  injection  of  pure  cultures  of  yeasts. 

It  appears  that  the  phagocytic  properties  of  the  saccharomycetes 
and  some  other  organisms,  were  known  to  Bruhat  and  De  Backer  as  far 
back  as  1892.  During  microscopical  examination  of  some  wine  that  had 
gone  wrong,  Bruhat  noticed  that  some  of  the  cells  of  the  ferment  (Saccharo- 
myces pastorianus)  had  included  in  them  other  cells,  viz.,  those  of  Bacillus 
aceti.  The  two  observers  then  instituted  a  series  of  experiments  for  the 
elucidation  of  this  phenomenon.  They  found  that  young  cells  of  most 
kinds  of  saccharomyces,  were  very  energetic  phagocytes  for  all  kinds 
of  bacteria,  englobing  and  digesting  them.  From  this  it  seemed  to 
follow,  if  Metchnikoff's  theory  of  immunity  were  correct,  that  organisms 
of  this  kind,  injected  into  the  blood  of  animals  infected  with  pathogenic 
microbes,  would  greatly  assist  the  leucocytes  in  their  phagocytic  work, 
provided  that  they  could  exist  in  the  blood  and  tissues  of  their  host, 
without  producing  ill-effects. 

To  test  the  practicability  of  this  method,  guinea-pigs  and  other 
animals  were  inoculated  with  the  ordinary  yeasts  of  commerce  ;  but, 
the  results  were  not  encouraging,  for  owing  to  the  presence  of  impurities 
the  yeasts  often  proved  pathogenic,  causing  abscesses  etc.  Pure  cultures 
of  Saccharomyces  cerevisice,  injected  with  aseptic  precautions,  were  there- 
fore substituted,  and  these  proved  innocuous.  The  animals  were  next 
injected  with  pure  cultures,  mixed  with  sterilized  fermentable  matter  ; 
and  experiments  were  made,  which  showed  that  under  these  circumstances 
fermentative  changes  occurred  within  the  body  of  the  animals  experi- 
mented upon,  which  were  none  the  worse  for  it.  Animals  infected  with 
bacterial  diseases,  were  next  treated  in  the  same  way.  Guinea-pigs 
infected  with  tuberculosis  and  diphtheria,  recovered  under  this  treatment. 

1  "De  la  Cancerose  et  de  son  Traitement  par  les  Ferments  purs."  Clermont  (Oise) ; 
also  "  The  Ferment  Treatment  of  Cancer  and  Tuberculosis,"  H.  Manders,  London,  1898. 


THE  MICROBIC  THEORY  OF  CANCER  259 

The  plan  was  then  tried  on  man.  Bruhat,  offering  himself  for  experi- 
mentation, was  injected  in  the  flank.  At  the  end  of  five  hours  a  chill 
occurred,  followed  by  sweating  and  symptoms  of  mild  intoxication.  At 
the  end  of  three  days  the  reaction  had  quite  ceased,  and  no  harm  resulted. 
The  infection  caused  leucocytosis.  Phthisical  patients  were  next  inocu- 
lated, and  it  is  claimed  that,  in  early  cases,  the  disease  was  nearly  always 
arrested  ;  and  most  other  cases  improved,  the  main  condition  for  success 
being  that  the  cultures  inoculated  shall  be  absolutely  pure. 

In  the  treatment  of  malignant  tumours  De  Backer  claims,  with  this 
method,  to  have  achieved  astonishing  results :  of  sixty  cases  there  were 
eighteen  cures,  lasting  over  some  years  ;  and,  in  many  others,  the  pro- 
gress of  the  disease  was  markedly  retarded. 

Here  mention  may  be  made  of  the  fact  demonstrated  by  Pasteur, 
more  than  a  quarter  of  a  century  ago,  that  the  saccharomycetes  can  obtain 
every  requisite  for  their  growth  in  the  human  body,  except  that  their 
main  food,  sugar,  can  be  obtained  only  in  small  quantities.  This 
deficiency  explains  the  slow  growth  of  these  organisms  in  normal  animal 
bodies,  as  compared  with  their  rapid  growth  in  sugar-containing  media. 

To  explain  the  curative  effects  of  these  injections  in  malignant  tumours, 
De  Backer  makes  use  of  this  hint.  He  noticed  that  many  of  his  guinea- 
pigs,  which  had  lived  together  in  full  liberty,  while  subjected  to  a  long 
course  of  pure  yeast  injections,  got  very  fat  and  at  the  same  time  became 
sterile  ;  so  that,  even  when  occasionally  impregnation  did  occur,  the 
foetus  failed  to  develop.  He  conceived  that  this  sterility  was  due  to 
diminished  production  of  glycogenous  material  in  the  uterus  etc.,  con- 
sequent on  yeast  injections.  It  is  known  that  localities  specially  prone 
to  cancer,  such  as  the  uterus,  breast,  liver,  stomach  etc.,  are  normally 
rich  in  glycogen  ;  and,  as  Brault  and  others  have  shown,  all  malignant 
tumours  are  also  remarkably  rich  in  this  material,  which  is  said  to  be 
absent  from  granulomatous  inflammatory  new  formations.  Moreover, 
we  know  that  the  blood  of  cancer  patients  is  also  unusually  rich  in  sugar- 
forming  substances. 

With  these  points  in  view,  De  Backer  concluded  that  blastomycetes 
artificially  introduced  into  the  body,  by  using  up  its  glycogen  for  their 
own  growth,  might  check  the  pathological  increase  of  this  substance  ; 
and  so  starve  the  young  cancer  cells,  by  depriving  them  of  their  essential 
nutriment.  Thus  the  whole  tumour  would  shrink  ;  for,  as  Brault  had 
shown,  the  rapidity  of  the  increase  of  malignant  tumours  was  directly 
proportional  to  the  amount  of  glycogen  they  contained. 

In  this  connexion,  it  is  interesting  to  note,  that  of  late  many  instances 
of  the  association  of  malignant  tumours  with  diabetes  have  been  reported 
(Kappler,  Boas,  Kreutzmann,  Tuffier,  and  others)  ;  and,  most  of  those 
who  have  specially  studied  this  subject,  maintain  that  the  diabetic  state 
favours  the  development  of  malignant  disease.1 

It  may  be  said  to  be  established,  as  the  outcome  of  these  and  other 
experiments,  that  injections  of  yeast  produce  leucopenia,  which  is  rapidly 
followed  by  leucocytosis  ;  with  consequent  large  increase  in  the  antiseptic 
substances,  normally  present  in  the  blood-serum. 

1  For  some  further  remarks  on  this  subject,  vide  Chapter  XVI. 

17—2 


260  THE  NATURAL  HISTORY  OF  CANCER 

Mould-like  Fungi. 

Even  as  far  back  as  1879,  I  became  aware  of  the  fact  that  mould-like 
fungi  grow  readily  in  human  tumours.  This  was  particularly  impressed 
on  my  memory  by  a  case  that  came  under  my  notice  in  that  year,  in  the 
clinic  of  Broca,  at  the  Necker  Hospital  in  Paris. 

The  patient  was  a  woman,  aged  fifty-eight,  with  a  large,  eroded, 
fungating,  cauliflower-like  tumour  of  the  right  breast.  A  lump  had 
appeared  in  the  breast,  after  her  last  confinement,  nineteen  years  pre- 
viously :  eight  years  later,  this  heretofore  comparatively  stationary  lump 
began  to  enlarge,  the  overlying  skin  ulcerated,  and  the  tumour  soon 
afterwards  fungated  ;  the  protruding  mass  was  then  cut  off,  but  it 
soon  grew  again  ;  and  the  present  tumour  was  the  gradual  outcome  of  this 
recrudescence.  On  examination  this  tumour  was  firm  and  non-adherent 
to  the  chest  wall ;  the  nipple  was  not  retracted  ;  and  there  was  no  enlarge- 
ment of  the  adjacent  lymph-glands.  The  diagnosis  was  fungating  fibroma 
of  the  mamma.  The  breast  with  the  tumour  was  removed.  Histological 
examination  showed  that  the  real  tumour  growth  consisted  of  fibro- 
cellular  tissue,  in  which  were  embedded  small  cysts,  lined  by  a  single  layer 
of  cubical  epithelium,  evidently  derived  from  the  ducts  of  the  mamma. 
The  histological  report,  by  Latteux,  of  which  I  still  have  a  copy,  says 
the  appearances  exclude  the  idea  of  sarcoma  :  "  C'est,  en  somme,  un 
fibrome  en  voie  de  developpement,  tumeur  essentiellement  benigne." 

Now,  the  whole  of  the  extensive  surface  of  the  fungating  part  of  this 
tumour,  was  covered  by  a  thick  layer  of  coarsely  mammillated  granulation 
tissue  ;  which  was  pervaded  throughout,  to  a  considerable  depth,  by  the 
mycelium  and  spores  of  a  mould  fungus, — of  which  Latteux's  report 
gives  a  good  sketch — although  no  trace  of  this  parasite  was  noticeable 
to  the  naked  eye. 

The  fungus  was,  of  course,  regarded  as  a  mere  epiphyte  ;  for,  at  that 
time,  no  one  thought  of  ascribing  the  origin  of  tumours  to  such  parasites. 

In  comparatively  recent  times,  instances  of  spontaneously  occurring 
granulomatous  pseudo-plasms  due  to  the  mould-like  fungi,  have  been 
met  with  in  the  skin  (Schamberg,  Ricketts,  Delepine  etc.),  and  in  the 
gastric  mucosa  (Max  Einhorn)  ;  and  similar  tumours  have  been  artificially 
produced  by  injection  of  pure  cultures  of  various  mould-like  organisms 
(Charrin  and  Le  Play,  Roth  well  etc.). 

An  interesting  case  of  this  kind,  which  had  been  diagnosed  after 
histological  examination  as  "  myeloid  sarcoma,"  has  lately  been  reported 
by  Coley  and  Tracy.1 

So  far  as  I  know,  Bra2  ("  Le  champignon  parasite  du  cancer")  was 
one  of  the  first  to  ascribe  the  causation  of  cancer,  to  the  presence  of 
organisms  of  this  kind.  By  culture  methods,  he  isolated  from  malignant 
epithelial  and  connective-tissue  tumours,  of  various  parts  of  the  body, 
as  well  as  from  the  blood  of  the  patients,  a  specific  cancer  microbe,  which 
he  regards  as  an  "  ascomyces."  His  cultures  were  made  by  insemination 
of  portions  of  the  tumours,  and  by  inoculations  from  the  blood  of  affected 

1  Journal  of  Medical  Research,  1907,  vol.  xvi.,  Xo.  2. 

2  C.  R.  Acad.desSci.,  Paris,  1900, t.  cxxxi.,  p.  1012;  also  LaPresse  Med.,  1899,  vii.,  p.  87. 


THE  MICROBIC  THEORY  OF  CANCER  261 

persons.  The  medium  used  was  cow's  udder  bouillon,  and  the  culture 
appeared  as  a  scum  and  a  sediment,  after  from  five  to  eight  days'  incuba- 
tion at  86°  to  95°  F. 

The  organism  was  of  spheroidal  or  cylindrical  form,  and  multiplied 
chiefly  by  sporulation,  mycelia  being  formed.  In  dogs  and  rabbits,  inocu- 
lated subcutaneously  with  these  cultures,  tumour-like  swellings  were  pro- 
duced, which  histologically  resembled  malignant  tumours — epitheliomata 
and  sarcomata.  By  inoculating  a  bitch  in  the  mammary  region,  Bra 
claims  thus  to  have  produced  typical  mammary  carcinoma.  From  these 
artificially  produced  tumours,  pure  cultures  were  made,  which  contained 
organisms  just  like  those  found  in  the  original  tumour.  The  inoculations 
into  guinea-pigs  proved  inert. 

Curtis l  of  Lille,  who  repeated  Bra's  experiments,  declares  that  after 
having  taken  precautions  to  eliminate  extraneous  organisms  and  other 
sources  of  error,  neither  cultures  nor  inoculation  results  could  be  obtained. 
He  found  that  all  tumours,  even  when  not  ulcerated  and  not  contiguous 
to  a  free  surface,  nevertheless  teemed  with  microbes  ;  while  ulcerated 
tumours  simply  swarmed  with  innumerable  kinds  of  microbic  life.  He 
concludes  that  human  cancers  are  neither  cultivable  nor  inoculable ;  and 
that  experiments  hitherto  published  to  the  contrary,  are  due  to  errors 
of  technique  etc. 

Niessen,2  while  examining  the  blood  of  a  woman  with  advanced 
uterine  cancer,  found  in  it  an  organism,  which  he  believed  to  be  the 
cause  of  the  disease.  In  this  blood  a  dark  green  mould  developed,  which 
was  cultivable.  It  proved  to  be  an  unknown  species  of  organism,  inter- 
mediate between  a  mycete  and  a  mould.  It  grew  with  great  luxuriance 
in  human  blood,  in  sterile  diabetic  urine,  and  in  water  ;  and  the  products 
of  the  cultures  in  these  different  media  were  themselves  so  diverse,  that 
it  was  difficult  to  believe  they  were  derived  from  the  same  source.  This 
organism  Niessen  named  Canceromyces  or  Cladosporum  cancer ogenes. 

Braithwaite,3  as  the  result  of  histological  examination  of  sections  of 
malignant  tumours,  found  the  morbid  tissues  pervaded  by  the  spores 
and  mycelia  of  a  mould-like  organism,  which  he  regarded  as  the  cause 
of  the  disease.  Fungoid  parasites  were  nearly  always  present  in  the 
specimens  he  examined  ;  and  he  claims  to  have  discriminated  eight  or 
nine  different  kinds  of  them  in  various  forms  of  cancer,  each  corresponding 
to  a  particular  variety  of  malignant  disease.  Braithwaite  has  also  found 
fungoid  organisms  in  non- malignant  growths  (e.g.,  uterine  myoma)  ; 
hence,  he  conjectures  that  non-malignant  tumours  may  also  be  of 
parasitic  origin 


General  Conclusions  as  to  Blastomycetes  etc. 

Amid  the  hubbub  of  conflicting  statements  as  to  the  relation  of 
blastomycetes  and  malignant  tumours,  we  may,  I  think,  discriminate 
the  following  propositions  : — 

1.  Certain  blastomycetes  are  pathogenic  for  man  and  animals,  and 

1  Lancet,  1899,  vol.  i.,  p.  801. 

2  Cent.  f.  d.  med.  Wissenscliaften,  Xr.  21,  1894.  3  Lancet,  June  29,  1895. 


262  THE  NATURAL  HISTORY  OF  CANCER 

they  may  even  cause  in  them  lesions,  which  in  their  gross  features  some- 
what resemble  malignant  disease.  Thus,  instances  of  pseudo-sarcomatous 
tumours,  due  to  the  presence  of  organisms  of  this  kind,  have  been  reported 
in  mankind  by  Curtis,  Busse,  Coley  etc.  ;  while  quasi-epitheliomatous 
lesions  of  similar  origin,  have  been  met  with  by  Gilchrist,  Owens,  Hyde, 
Hektoen,  and  others.  It  also  appears  that  certain  oidia  (Obici,  Ricketts), 
aspergilli  (Renon,  Saxer,  Boyce,  Rothwell),  bothryomycetes  (Delore, 
Poncet),  and  probably  other  organisms,  may  originate  similar  morbid 
conditions. 

That  tumour-like  swelh'ngs,  which  are  often  confounded  with  sar- 
comata, may  be  caused  by  actinomycetic  infection,  is  now  generally 
admitted  by  pathologists.  Moreover,  tumours  of  this  kind  are  not 
particularly  rare,  and  they  have  been  seen  in  almost  every  part  of  the 
body.  As  Wolff  and  Israel  have  shown,  pure  cultures  of  these  organisms, 
injected  into  rabbits,  give  rise  to  tumour-like  swellings. 

When  carefully  examined,  these  parasitic  pseudo -plasms  are  found  to 
differ  markedly  from  true  malignant  tumours,  both  structurally  and  in 
their  clinical  features  ;  and  they  should  evidently  be  classed  with  the 
infective  granulomata. 

In  consequence  of  these  important  discoveries,  certain  anomalous 
pseudo-malignant  lesions,  which  have  long  puzzled  pathologists  and 
clinicians,  may  now  be  moved  from  the  category  of  malignant  neoplasms 
into  that  of  the  parasitic  infections. 

2.  So   many  pathologists   have   succeeded   in   obtaining   pure   cul- 
tures of  blastomycetes  from  human  malignant  tumours,  that  I  regard 
the  liability  of  the  latter  to  blastomycetic  infection  as  having  been 
proved,  although  not  a  few  investigators  have  failed  to  get  positive 
results.     Considering  the  richness   of  these  tumours  in  sugar-forming 
materials,  which  are  so  favourable  to  the  growth  of  blastomycetes,  it 
would  indeed  be  strange  if  they  were  not  more  prone  to  this  kind  of 
infection  than  the  normal  tissues  of  the  body. 

3.  In  their  young  and  nascent  condition,   it   has  been  repeatedly 
demonstrated,  notwithstanding  many  assertions  to  the  contrary,  that 
non-ulcerated  malignant  tumours  are  quite  free  from  blastomycetes. 

4.  The  repeated  failures  to  produce  malignant  tumours  in  animals, 
by  inoculation  experiments  with  cultures  of  blastomycetes,  prove  that 
the  latter  cannot  be  the  specific  causative  factor  of  malignant  disease. 
The  few  instances  in  which  it  is  alleged  that  malignant  tumours  have 
been  thus  caused  (Sanfelice,  Bra,  Leopold  etc.),  are  capable  of  being 
otherwise  explained  (blastomycetic  or  other  granulomata,  spontaneously 
arising  malignant  disease  etc.)      The  ensemble  of  many  experiments 
clearly  shows,  that  yeast  organisms  etc.,  are  incapable  of  causing  the 
formation  of  true  malignant  neoplasms  (epithelioma  and  sarcoma). 

The  Question  of  Infection. 

In  previous  chapters,1  I  have  already  had  occasion  to  refer  to  the 
subject  of  infection  ;  but,  to  complete  the  matter,  some  aspects  of  this 
important  question  still  remain  to  be  studied. 
1  Chapters  IV.  and  VIII. 


THE  MICROBIC  THEORY  OF  CANCER  263 

In  comparatively  recent  times,  attempts  have  been  made  to  utilize 
the  irregularities  invariably  met  with  in  the  topographical  distribution 
of  cancer,  as  evidence  of  the  infectious  nature  of  the  disease  ;  which,  it 
is  alleged,  may  manifest  epidemic,  endemic,  and  even  pandemic  char- 
acters. Hence,  we  now  often  hear  of  "  cancer  districts,"  "  cancer  houses," 
and  even  of  "  cancer  rooms." 

Arnaudet  *  was  the  first,  who  formulated  ideas  of  this  kind.  In 
certain  remote  rural  districts  in  Normandy,  he  found  that  cancer  was 
twice  or  thrice  as  prevalent  as  in  Paris,  where  the  disease  is  of  great 
frequency  ;  thus,  in  the  little  hamlet  of  St.  Sylvestre  de  Cormeilles,  the 
cancer  mortality — for  a  period  of  eight  years — averaged  no  less  than 
14-88  per  cent,  of  the  total  deaths.  He  also  adduced  instances  of  cancers 
coexisting  in  various  organs  of  persons  living  in  certain  houses  or  in 
their  vicinity.  Hence,  he  concluded  that  the  locality  where  a  cancer 
patient  had  lived  was  contaminated  ;  and  he  thought  it  probable  that 
the  contagion  was  spread  chiefly  through  drinking  polluted  pond-water, 
which  also  contaminated  the  local  cider,  etc.  Similar  instances  were 
soon  afterwards  advanced  by  Sorel,  Guelliot,  Fabre,  Fiessinger,  Webb, 
D'Arcy  Power,  Behla  and  others. 

Webb  2  reported  the  following  remarkable  group  of  cases  : 

In.  a  village  not  far  from  his  residence  were  two  houses  under  one  roof, 
with  water-supply  and  drainage  in  common.  Let  us  call  them  Nos.  1 
and  2.  Twenty-six  years  ago  a  man  aged  twenty-eight,  living  in  No.  1, 
died  of  cancer  of  the  rectum.  Mr.  J.  H.  and  his  wife  next  occupied  this 
house.  His  age  was  then  sixty.  Two  years  later  he  died  of  cancer  of 
the  stomach.  His  widow,  who  continued  to  live  in  the  same  house,  died 
in  it  ten  years  later  of  cancer  of  the  rectum. 

Prior  to  her  death,  Mrs.  R.,  aged  fifty,  who  lived  in  No.  2,  was  found 
to  have  cancer  of  the  breast,  which  ended  fatally  eight  months  later. 

After  the  death  of  Mrs.  J.  H.,  No.  1  was  occupied  by  three  maiden 
ladies.  Of  these,  Miss  P.  died  four  years  ago,  aged  fifty-eight,  of  cancer 
of  the  uterus  ;  Miss  F.,  who  nursed  her,  died  last  winter,  aged  sixty-one, 
of  cancer  of  the  stomach  ;  the  other  sister  was  still  alive  and  well. 

None  of  these  persons  were  blood  relatives  ;  and,  in  none  of  the 
families,  was  there  a  history  of  cancer  in  other  relatives. 

In  support  of  the  infectious  nature  of  the  disease,  it  is  alleged  that  the 
dwellers  in  certain  houses,  and  even  in  certain  rooms,  may  become  affected 
with  cancer,  either  simultaneously  or  successively,  with  undue  frequency  ; 
that  instances  of  the  disease  attacking  two  persons  living  together  (cancer 
d  deux)  are  relatively  frequent ;  and  that,  in  certain  localities,  so  many 
cases  may  be  met  with  as  to  constitute  veritable  epidemics. 

Fiessinger  3  has  met  with  several  examples  of  such  outbreaks. 

Thus,  in  a  small  village,  a  woman  died  of  cancer  of  the  breast,  and 
within  a  comparatively  short  space  of  time,  two  other  women  lodging 
in  the  house  died  of  the  same  disease — one  of  the  rectum  and  the  other 

1  Nortnandie  Med.,  1890,  iv.,  p.  33;  also  L' Union  Med.,  Ap.  25,  1889;  Normandie 
31ed.,  Ap.  1  and  Ap.  15,   1890;  also  Feb.  15,  1891.      "  Xouveaux  faits  k  1'appui  de  la 
nature  infectieux  du  cancer." 

2  Birminghsim  Medical  JReview,  1892,  vol.  xxxii.,  p.  342;  also  ibid.,  1894,  vol.  xxxvi., 
p.  209.  3  Jkvue  de  Mid.,  January,  1893. 


264  THE  NATURAL  HISTORY  OF  CANCER 

of  the  vulva  ;  and,  after  a  certain  time,  two  neighbours  also  died — one 
of  cancer  of  the  stomach,  and  the  other  of  sarcoma  of  the  leg. 

He  believes  that  these  "  epidemics  "  are  particularly  apt  to  occur  on 
the  banks  of  rivers,  at  the  borders  of  woods  etc.,  and  he  suggests  that 
insects,  which  are  plentiful  in  such  places,  are  concerned  in  disseminating 
the  disease,  as  well  as  contaminated  fingers  etc. 

Guelliot l  of  Reims  has  reported  forty  cases,  in  which  malignant  disease 
appeared  to  have  been  spread  by  contagion.  He  claims  to  have  proved  : 
(1)  that  malignant  disease  is  unequally  distributed  in  adjoining  districts, 
in  such  a  manner  that  neither  heredity  nor  consanguinity  will  account 
for  it ;  (2)  that  there  are  real  "  cancer  houses,"  the  dwellers  in  which,  in 
the  absence  of  blood  relationship,  are  nevertheless  successively  or  simul- 
taneously attacked  by  malignant  tumours  ;  (3)  that  cases  of  malignant 
disease  attacking  two  persons  living  together  are  relatively  frequent ; 
and  (4)  that  of  one  hundred  such  cases,  eighty-five  were  man  and  wife, 
and  eight  were  medical  practitioners,  who  had  been  engaged  in  the  treat- 
ment of  cases  of  malignant  disease.  According  to  Guelliot,  these  facts 
show  that  cancer  is  an  infectious  disease,  which  is  transmitted  directly 
or  indirectly  by  contagion.  It  is  alleged  that  cancer  is  prone  to  occur 
in  damp,  low  -  lying  situations,  in  the  vicinity  of  sluggish  streams, 
in  marshy  areas,  in  localities  prone  to  floods,  in  sewage-saturated  regions, 
in  places  having  a  retentive  subsoil,  such  as  clay,  in  the  vicinity  of  trees 
etc.  ;  and  that  this  infection  is  spread  by  water,  uncooked  vegetables, 
insects,  domestic  animals  etc. 

D'Arcy  Power  2  claims  to  have  demonstrated  localized  epidemics  of 
cancer  in  certain  districts,  villages,  houses,  and  "  even  in  a  single  room  "; 
but,  beyond  the  bald  narration  of  certain  exceptional  occurrences,  which 
of  themselves  are  by  no  means  convincing,  he  has  not  even  attempted  to 
prove  his  thesis. 

Bosc,3  having  noticed  the  frequency  of  parasites  and  parasitic  tumour- 
like  swellings  in  fishes,  believes  that  many  outbreaks  of  cancerous  disease 
are  due  to  this  cause.  He  thinks  that  gastro-intestinal  cancer  is  often 
caused,  by  the  bones  of  small  fish  wounding  parts  of  the  alimentary  canal. 
External  cancers,  he  maintains,  are  often  due  to  infection  carried  by 
insects  and  various  animals  ;  by  contaminated  fingers  and  polluted  water  ; 
and  even  by  fleas,  bugs,  flies  etc. 

In  a  previous  chapter,4  I  have  referred  to  Haviland's  interesting 
researches,  as  to  the  influence  of  local  geological  and  topographical  con- 
figuration in  the  incidence  of  cancer  ;  and  I  have  there  explained  my 
reasons  for  being  unable  to  give  them  more  than  a  certain  limited  accept- 
ance. 

In  1899,  a  committee  appointed  by  the  Birmingham  Branch  of  the 
British  Medical  Association,5  investigated  the  influence  of  locality  on 
the  incidence  of  malignant  tumours,  in  parts  of  Warwickshire,  Stafford* 

1  Oaz.  des  Hdpitaiix,  1892,  No.  139. 

2  British  Medical  Journal,  1894,  vol.  i.,  pp.  1240  and  1302;  ibid.,  April  27,  1895; 
also  Edinburgh  MedicalJournal,  1902,  vol.  xii.,  p.  39. 

3  "Le  Cancer,"  Paris,  1898.  *  Chapter  IV. 

6  British  Medical  Journal,  1899,  vol.  i.,  p.  812  ;  also  Birmingham  Medical  Bevieic, 
May,  June,  and  July.  1900. 


THE  MICROBIC  THEORY  OF  CANCER  265 

shire,  Shropshire  and  Worcestershire.  They  concluded,  that  there  were 
districts  in  which  this  disease  occurs  with  frequency  much  above  the 
average,  side  by  side  with  other  districts  in  which  it  is  rare.  The  high- 
mortality  districts  were  usually  poorly  drained,  flat,  low-lying  or  border- 
ing on  streams  ;  whereas  the  low-mortality  districts,  were  high,  dry,  and 
well  drained.  They  believe  that  there  is  a  direct  connexion  between  the 
presence  of  subsoil  water  within  a  certain  distance  of  the  surface,  and 
the  prevalence  of  malignant  disease. 

They  also  found  that  second  and  third  cases  of  cancer  occur  in  par- 
ticular houses,  more  frequently  than  can  be  accounted  for  by  coinci- 
dence ;  that  particular  groups  of  houses,  perhaps  in  the  same  street,  may 
be  similarly  affected  ;  and  they  suggest  that  this  association  implies 
contaminated  soil.  Old  houses  also  appeared  to  furnish  a  higher  pro- 
portion of  cancer  cases,  than  new  ones. 

Scott,1  after  having  studied  the  prevalence  of  cancer  in  the  Chelmsford 
and  Maldon  districts  of  Essex,  concluded  that  whatever  truth  may  underlie 
Haviland's  theory,  it  is  insufficient  to  explain  the  distribution  of  cancer 
in  these  parts.  Essex  is  a  flat,  marshy  county,  with  a  clayey  subsoil,  and 
it  used  to  be  the  home  of  malaria  ;  yet  the  cancer  death-rate  for  the 
county  is  by  no  means  high,  being  below  the  average  for  England  as  a 
whole.  Although  the  unions  of  Chelmsford  and  Maldon,  contain  an 
excessive  proportion  of  marshy  land  and  estuary  ("  saltings  ")  ;  yet,  their 
cancer  death-rate,  is  less  than  that  of  the  whole  county.  Those  parts  of 
the  two  unions  which  include  the  greatest  extent  of  muddy  foreshore, 
creek,  and  "  saltings,"  have  a  smaller  cancer  mortality,  than  that  of  the 
whole  of  the  two  unions  taken  together.  The  disease  was  found  not  to  be 
specially  prevalent,  in  places  situated  on  the  banks  of  the  fresh-water 
rivers.  In  these  parts  of  Essex,  therefore,  the  cancer  mortality  bears  no 
evident  relation  to  the  variations  in  the  physical  features  of  the  country. 

Noel2  finds  that  in  "  cancer  districts  "  certain  contagious,  tumour- 
like  growths  are  often  seen  on  the  trees,  which  have  a  certain  resemblance 
to  malignant  tumours.  He  thinks  that  between  these  "  arboreal  cancers  " 
and  human  malignant  disease,  there  is  some  aetiological  connexion,  for 
the  latter  are  of  frequent  occurrence  in  persons  living  surrounded  by  or 
near  woods.  Cancer  of  the  lip,  he  says,  never  originates  in  Lyons  ; 
but  all  those  having  the  disease  in  that  city,  are  found  to  have 
contracted  it  in  the  country.  Noel  considers  it  as  proved  that  insects, 
especially  certain  wasps,  have  a  special  predilection  for  "  arboreal 
cancers  "  ;  and  that  they  carry  the  infection  not  only  from  tree  to  tree, 
but  also  disseminate,  it  (through  orchards  etc.)  in  human  foods.  He 
maintains  that  human  beings  may  thus  be  infected  ;  when  the  contagion 
enters  by  the  mouth,  gastro -intestinal  lesions  result,  while  external  parts 
are  attacked  through  contact  infection. 

Behla 3  believes  that  cancer  is  a  parasitic  disease,  which  may  be 
propagated  like  malaria  ;  and  both  maladies  have,  he  thinks,  some  relation 

1  British  Medical  Journal,  1900,  vol.  ii.,  p.  420. 

2  "  Sur  la  topographic  et  la  contagion  du  cancer,"  Rev.  des  Mai.  Cancereuses,  Paris, 
1896-1897,  ii.,  pp.  137  and  201  ;  also  These  de  Paris,  1897. 

3  Cent.  f.  Bakt.,  etc.,  1898,  Bd.  xxiv.,  pp.  780,  829,  875,  and  919 ;  also  Zeits.  f.  Hygiene, 
1899,  Bd.  xxxii.,  p.  123,  etc. 


266  THE  NATURAL  HISTORY  OF  CANCER 

to  damp,  marshy  conditions  of  soil.  But  differences  in  the  soil,  in  the 
well-water,  or  in  the  atmospheric  conditions,  cannot  account  for  such 
diversities  in  the  incidence  of  the  disease,  as  he  has  noted  in  different 
sections  of  the  small  agricultural  town  of  Luckau  ;  thus,  only  the  food 
remains.  The  inhabitants  of  the  suburb  in  which  cancer  is  so  prevalent, 
are  mainly  small  farmers  and  nursery-men,  who  eat  large  quantities  of 
the  uncooked  vegetables,  which  they  raise — cabbages,  radishes,  water- 
cress, lettuces  etc.  Behla  then  points  out,  that  these  plants  are  liable 
to  tumour-like  diseases  of  parasitic  origin,  such  as  that  caused  in  cabbages 
by  Plasmodiophora  brassicce.  He  has  found  drinking-water  and  vegetables 
teeming  with  these  parasites,  which  he  maintains  are  the  infective  agents 
of  human  cancer.  The  great  frequency  of  gastro-intestinal  cancer, 
points  to  the  food  as  the  chief  means  by  which  the  contagion  enters  the 
body. 

The  domestic  animals — such  as  dogs  and  cats — as  well  as  the  rats  and 
mice  of  Luckau,  are  prone  to  cancerous  tumours  ;  and,  Behla  thinks  that 
these  animals  may  also  be  a  source  of  contagion,  by  which  the  malady  is 
communicated  to  mankind.  He  also  claims  to  have  proved  that  cancer 
clings  to  certain  streets,  houses,  or  groups  of  buildings,  irrespective  of 
their  size  and  age. 

Behla  has  made  special  study  of  the  house  incidence  of  all  cancer 
deaths  in  Luckau — which  comprises  a  stationary  population  of  5,000 — for 
a  period  of  twenty-two  and  a  half  years.  During  this  period,  about  1  in 
25  of  the  total  deaths  for  the  whole  town  were  due  to  cancer,  which  is 
not  a  very  high  ratio. 

The  central  part  of  Luckau,  which  is  low-lying  and  surrounded  by 
ditches,  comprising  3,000  inhabitants,  furnished  65  cancer  deaths.  Of 
its  415  houses,  in  33  there  had  been  a  single  cancer  death  ;  in  10,  two 
such  deaths  ;  and  in  4,  three  cancer  deaths. 

Its  eastern  suburb  Kalau,  which  is  also  low-lying  and  marshy,  being 
intersected  by  irrigation  channels  for  market-gardening,  comprising 
1,000  inhabitants,  furnished  73  cancer  deaths,  or  1  in  9  of  its  total  mor- 
tality. Of  its  127  houses,  in  45  there  had  been  a  single  cancer  death  ;  in  9, 
two  cancer  deaths ;  in  2,  three  such  deaths  ;  and  in  1,  four  deaths.  The 
cancer  mortality  of  this  suburb  was  fourfold  that  of  the  central  part  of 
Luckau.  Of  the  40  houses,  comprising  its  main  street,  only  5  were 
without  at  least  one  cancer  death  ;  and  56  of  the  total  73  cancer  deaths, 
occurred  in  the  houses  of  this  street. 

In  curious  contrast  with  the  foregoing,  the  high-lying  and  dry  suburb 
of  Sando,  comprising  1,000  inhabitants,  had  not,  a  single  death  from 
cancer  during  the  whole  twenty-two  and  a  half  years. 

In  estimating  the  value  of  these  data  it  must  be  borne  in  mind,  that 
no  information  is  given  as  to  the  social  condition,  age  and  sex  distribution 
of  the  contrasted  populations,  which  alone  might  suffice  to  explain  much 
of  these  diversities,  judging  by  the  experience  gained  as  to  the  cancer 
mortality  of  such  places  as  Hampstead,  Clifton  and  Bath,  to  which  I  have 
previously  referred ;  moreover,  the  same  reticence  is  manifest  with 
regard  to  hospital  accommodation,  heredity,  and  the  method  of 
registration.  It  is  not  stated  what  proportion  of  those  attacked  with 


THE  MICROBIC  THEORY  OF  CANCER  267 

cancer,  in  each  of  the  respective  parts  of  the  town,  were  treated  and  died 
elsewhere  than  at  home.  Then,  again,  it  should  be  noted,  that  although 
the  investigation  comprised  a  series  of  years  ;  yet,  owing  to  the  small- 
ness  of  the  community,  the  massif  of  the  totals  is  far  too  small  to 
enable  reliable  averages  to  be  deduced  therefrom.  Hence,  as  evidence 
of  infection,  these  much-paraded  data  have  per  se,  but  little  scientific 
weight. 

From  study  of  the  cancer  incidence  in  the  Nuneaton  and  Stratford-on- 
Avon  districts,  E.  N.  Nason  x  concludes,  that  cases  of  cancer  tend  to  group 
themselves  chiefly  in  the  vicinity  of  sluggish  streams,  and  where  the 
subsoil  is  indifferently  drained,  sewage-polluted  etc. 

Lloyd  Jones 2  has  worked  out  the  local  distribution  of  malignant 
disease  in  Cambridge  and  its  vicinity,  during  a  period  of  nineteen  years. 
He  concluded  as  follows  :  (1)  that  some  parts  of  the  town  are  compara- 
tively free  from  the  disease,  while  other  parts,  often  contiguous,  suffer 
severely  ;  (2)  that  elevated  sites  are  less  liable  than  low-lying  ones  ; 
(3)  that  the  chalk  subsoil  is  the  freest  from  the  disease  ;  (4)  that  proximity 
to  the  river  is  not  always  attended  by  a  high  cancer  death-rate,  although 
damp  sites  favour  the  disease  ;  (5)  that  proximity  to  trees,  especially  large 
ones,  in  some  way  favours  the  prevalence  of  cancer  ;  (6)  that  decaying 
vegetation,  filth,  collections  of  manure  etc.,  are  often  found  in  cancer 
districts. 

Mason  3  has  in  like  manner  examined  the  problem  of  cancer  distribu- 
tion, for  the  Leamington  district  of  Warwickshire.  He  believes,  whatever 
the  ultimate  cause  of  the  disease  may  be,  that  it  will  be  found  to  be 
associated  with  a  sewage-contaminated  subsoil ;  that  end  houses  of  rows, 
corner  houses  of  streets,  and  houses  on  either  side  of  court-entries  are 
often  "  cancer  houses,"  owing  to  drain  leakages  and  consequent  sewage 
contamination  being  most  frequent  at  those  spots  ;  that  old  houses  are 
more  dangerous  than  modern  ones  for  the  same  reason  ;  and  that  houses 
built  on  porous  subsoil  (sandstone,  gravel  etc.),  are  more  prone  to  favour 
the  development  of  cancer  than  those  built  on  clay. 

Gifford  Nash,4  from  the  study  of  the  distribution  of  cancer  in  North 
Bedfordshire,  has  arrived  at  the  following  conclusions  : — 

1.  That  the  occurrence  of  cancer  in  that  district,  is  a  little  above  the 
average  for  England  and  Wales. 

2.  That  cancer  appears  to  be  less  common  in  the  urban,  than  in  the 
rural  districts. 

3.  That  the  liability  of  the  disease  to  attack  the  alimentary  system  is 
very  great. 

4.  That  the  percentage  of  cases  at  an  elevation  of  300  feet,  is  con- 
siderably greater  than  under  150  feet ;  and  also  greater  than  that  of  the 
villages  adjacent  to  the  river  Ouse.     Hence  proximity  to  the  river,  low 
elevation,  liability  to  floods  etc.,  does  not  increase  the  tendency  to  cancer. 

5.  That  the  nature  of  the  soil  appears  to  have  very  little  influence  on 
the  occurrence  of  cancer. 

1  British  Medical  Journal,  1898,  vol.  i.,  p.  679. 

2  Ibid.,  1899,  vol.  i.,  p.  813.  3  Ibid.,  1902,  vol.  i.,  p.  139. 

4  "Cancer,  with  special  reference  to  its  distribution  in  North  Bedfordshire,"  1903. 


268  THE  NATURAL  HISTORY  QF  CANCER 

6.  That  the  large  number  of  instances  in  which  two  or  more  cases 
occurred  in  the  same  house,  or.  in  persons  intimately  associated,  points  to 
the  disease  being  infectious. 

7.  That  infection,  if  it  exists,  is  a  very  slow  one,  the  usual  interval 
between  two  cases  in  the  same  house  and  family,  being  about  two  years  ; 
and  the  liability  to  infection  increases  with  age,  very  few  cases  occurring 
under  forty  years. 

Symons  l  has  made  a  careful  inquiry  as  to  the  relation  of  cancer  to 
the  dwelling-house,  as  met  with  in  Bath,  a  town  of  about  50,000  inhabi- 
tants, which  has  a  high  and  progressive  cancer  mortality,  with  a  low  and 
diminishing  tubercle  death-rate.  Its  population,  of  whom  two-thirds 
are  females,  has  been  stationary  for  the  last  half-century.  This  excess 
of  females  is  largely  due  to  the  number  of  young  women,  employed  as 
domestic  servants  etc.  The  population  of  Bath  also  comprises  an 
unusually  high  proportion  of  middle-aged  and  elderly  persons,  especially 
females  ;  and  comparatively  few  children  under  five  years  old.  Another 
of  its  peculiarities  is  the  well-to-do-ism  of  its  inhabitants,  the  proportion 
of  persons  of  "  independent  means  "  residing  there,"  exceeding  that  of  any 
other  town  in  England.  Its  general  health  and  sanitary  conditions  are 
good,  typhoid  fever  and  infectious  diseases  are  rare,  its  general  and 
tuberculous  death-rates  are  low,  and  in  all  these  respects  progressive 
improvement  is  noticeable  ;  yet  withal,  its  cancer  mortality  is  very  high, 
and  for  the  last  half-century  it  has  been  steadily  increasing,  until,  at  the 
present  time,  its  corrected  death-rate  from  this  cause  is  50  per  cent,  in 
excess  of  the  average  for  the  vicinity. 

This  city  is  situated  in  a  deep  valley — in  the  midst  of  hilly  country — 
which  is  traversed  by  a  sluggish,  sewage-contaminated  river,  prone  to 
flood  the  adjacent  lands  ;  it  has  a  dense  surface  soil,  overlying  lias  and 
oolite,  which  is  permeated  by  numerous  ground  springs,  the  water  being 
very  hard.  The  town  comprises  many  hills,  and  is  surrounded  and  some- 
what shut  in  by  them  ;  so  that,  although  most  of  the  houses  lie  in  the 
hollow,  many  are  built  on  the  slopes  of  the  hills,  and  most  of  the  best 
residential  houses  enjoy  quite  elevated  sites. 

In  order  to  get  at  the  facts,  as  to  the  precise  local  distribution  of 
malignant  disease  in  the  town,  Symons  located  houses,  1,212  in  number, 
in  which  1,319  deaths  from  this  cause  had  occurred  during  a  period  of 
thirty-two  years  (1866-1897),  among  8,507  houses.  Of  the  houses  in 
which  these  deaths  occurred,  the  great  majority,  viz.,  1,111,  had  only  a 
single  fatality  in  each  house  ;  in  95  houses  there  had  been  2  fatal  cases  ; 
and  there  were  6  houses  in  which  3  cancer  deaths  had  occurred.  These 
numbers  were  so  little  in  excess  of  those  that  the  usual  mathematical 
method  of  calculating  probabilities  indicated,  that  Symons  concluded 
neither  the  elevation,  nor  the  aspect,  nor  the  class  of  house,  had  any 
constant  relation  to  the  incidence  of  the  disease  ;  and  thus  it  was  proved, 
so  far  as  Bath  is  concerned,  that  there  are  no  "  cancer  houses  "  there. 

Applying  this    method  to   the  data  for  Cambridge,  as  compiled  by 
Lloyd  Jones — who  found  that  in  nineteen  years,  among  5,685  houses, 
438  had  harboured  persons  who  had  died  of  cancer,  of  which  only  7  houses 
1  Public  Health,  December,  1898. 


THE  MICROBIC  THEORY  OF  CANCER  269 

had  double  cases  and  3  triple  ones — Symons  showed  that  this  proportion 
of  multiple  fatalities  was  actually  less,  than  that  indicated  by  the  calcu- 
lated probabilities  ;  so  that  in  Cambridge,  as  in  Bath,  there  were  shown 
to  be  no  "  cancer  houses." 

Hence  Symons  concludes,  that  there  is  no  scientific  basis  for  the 
doctrine  of  "  cancer  houses." 


General  Conclusions  as  to  Infection. 

As  I  have  previously  indicated,  no  evidence  in  favour  of  infection  is 
forthcoming  from  any  of  the  large  hospitals,  in  which  numerous  cancer 
patients  are  constantly  under  treatment ;  nor  from  those  who  are,  in 
these  institutions,  constantly  in  close  contact  with,  their  inmates. 

It  accords  with  this,  that  we  never  hear  of  "  cancer  epidemics  " 
arising  in  the  overcrowded  parts  of  our  great  cities,  where  the  density  of 
population  is  at  its  maximum,  and  where  sanitation  is  least  regarded  ; 
but,  it  is  rather  from  remote,  sparsely  populated,  rural  districts,  that  all 
the  instances  of  this  kind  have  come. 

If  cancer  is  an  infectious  disease,  how  is  it  that  so  few  cases  occur 
until  after  middle  life  ;  whereas,  in  other  infectious  diseases,  it  is  the 
young  who  are  specially  predisposed  ? 

It  appears  to  me,  for  reasons  I  have  previously  set  forth,  that  variations 
in  the  incidence  of  cancer  mortality,  can  be  far  more  satisfactorily  ex- 
plained, as  the  outcome  of  divergent  conditions  of  existence,  rather  than 
as  the  result  of  infection. 

Indeed,  it  is  remarkable  that  a  high  local  cancer  mortality,  nearly 
always  coincides  with  and  is  indicative  of,  healthy  surroundings  ;  as  is 
evidenced  by  the  fact  that  there,  the  density  of  population  is  least,  the 
tubercle  mortality  lowest,  the  average  duration  of  life  longest,  the 
infantile  and  general  mortality  lowest,  while  infectious  diseases  are  at  a 
minimum  :  in  short,  among  the  wealthy  and  well-to-do,  where  the 
standard  of  health  is  at  its  best  and  life  is  easiest,  there  the  cancer 
mortality  is  highest. 

Of  this  in  London,  Hampstead  is  a  striking  example  ;  in  Bristol, 
Clifton  ;  and  in  Bath,  as  we  have  seen,  it  is  the  same. 

On  the  other  hand,  where  sanitary  conditions  are  least  regarded, 
where  the  struggle  for  existence  is  hardest,  the  density  of  population 
greatest,  and  infectious  diseases  are  most  prevalent ;  that  is  to  say,  among 
the  workers  of  our  large  towns,  there  the  cancer  mortality  is  lowest. 

It  accords  with  the  foregoing,  that  malignant  tumours  are  of  great 
rarity  in  early  life  ;  and,  at  this  period,  the  epithelial  form  of  the  malady 
is  practically  unknown  :  in  all  these  respects  malignant  tumours  differ 
from  infectious  maladies  in  general. 

As  against  these  weighty  considerations,  the  curious  medley  of  chaotic 
and  conflicting  statements,  advanced  by  the  advocates  of  infection  in 
support  of  their  thesis,  seem  to  me  to  be  of  little  worth.  We  need  not 
seriously  entertain  these  fairy  tales,  when  their  great  progenitor — the 
hypothetical  microbe  of  cancer — has  been  discovered. 


CHAPTER  XI 

INFLAMMATION,  TRAUMA,  AND  OTHER  EXTRINSIC  FACTORS 
Inflammation  and  Tumour  Formation. 

THE  leading  pathologists  of  the  nineteenth  century  were  more  profoundly 
divided,  as  to  the  essential  relations  of  inflammation  and  tumour  forma- 
tion, than  on  any  other  subject  of  the  first  importance  in  the  whole 
range  of  pathology  ;  but,  at  the  time,  not  much  was  said  about  it.  These 
divergences,  after  having  long  lain  comparatively  dormant,  have  now 
under  the  stimulus  of  modern  research  flamed  up  again,  in  such  a  manner, 
that  they  cannot  any  longer  be  ignored. 

In  a  previous  chapter,1  I  had  occasion  to  refer  to  the  peculiar 
position  taken  up  by  Virchow  in  this  matter  ;  how  that  he,  so  to  speak, 
ran  with  the  Broussaisian  hare,  and  hunted  with  the  Miillerian  hounds, 
as  if  the  processes  of  inflammation  and  growth  were  identical ;  whereas, 
as  I  shall  now  proceed  to  show,  they  are  in  every  respect  fundamentally 
different  and  distinct.  It  is  noticeable,  moreover,  that  Virchow's 
neoplastic  pathogeny  2  is  throughout  dominated  by  the  Broussaisian  con- 
ception, that  tumours  are  but  forms  of  inflammation  ;  whereas  the 
Miillerian  doctrine,  that  tumours  are  due  to  abnormal  growth,  is  used 
merely  as  a  subsidiary  hypothesis,  to  make  good  the  more  obvious  short- 
comings and  defects  in  the  dominant  hypothesis.  It  is  Virchow's 
neoplastic  pathogeny,  thus  vitiated  ab  initio  by  fundamental  misconcep- 
tion, that  the  microbists  have  revived  in  recent  times,  accentuating  its 
errors,  with  such  results  as  I  have  set  forth  in  the  preceding  chapter. 

The  leading  British  exponent  of  the  Broussaisian  doctrine  of  tumour 
formation  is  Jonathan  Hutchinson,3  who  has  formulated  his  views  as 
follows  :  "  The  propositions  in  reference  to  cancer,  which  I  am  chiefly 
concerned  to  maintain,  are  :  First,  that  it  is  a  modification  of  chronic 
inflammation,  and  that  the  same  laws  which  are  applicable  to  the  one 
are,  for  the  most  part,  applicable  to  the  other.  Second,  that  it  is  under 
the  influence  of  inherited  tendency  and  of  senility,  that  processes  inflam- 
matory in  their  outset  tend  to  pass  into  those  of  cancer.  Third,  that 
cancerous  processes  are  in  their  initiation  local,  and  that  the  disease 
becomes  constitutional  by  infection,  by  elements  derived  from  the 
primary  growth." 

Among  those  who  combated  the  fallacies  of  Virchow's  tumour  doc- 
trine were  Billroth  and  Cohnheim,  both  of  whom,  like  J.  Miiller,  rejected 

1  Chapter  VII. 

2  Die  krankhaften  Geschwulste,  Bd.  i. 

3  Archives  of  Surgery,  October,  1890,  p.  138. 

270 


INFLAMMATION,  TRAUMA,  AND  OTHER  FACTORS       271 

the  inflammation  theory.  "  A  tumour,"  says  Billroth,1  "  is  a  neoplasm 
that  has  not  started  from  the  same  causes  as  excite  inflammation  ;  but 
from  others  that  are  unknown,  or  but  vaguely  suspected." 

I  think  I  have  already  made  it  sufficiently  plain  both  in  tin's  and  in 
other  chapters,  that  my  views  on  this  important  matter  are  entirely  in 
accord  with  those  of  Miiller,  Billroth  and  Cohnheim  ;  indeed,  I  believe 
that  the  Broussaisian  doctrine  of  tumour  formation,  is  mainly  responsible 
for  the  comparatively  small  progress  that  has  been  made,  during  the  last 
half-century,  in  tumour  pathogeny — this  misconception  having  given  a 
wrong  bent  to  the  direction  of  tumour  research. 

For,  since  inflammation  is  the  outcome  solely  of  extrinsic  causes, 
whereas  the  causes  winch  determine  tumour  growth  are  mainly  intrinsic, 
it  is  obvious  that  of  these  divergent  and  incompatible  ways,  only  one 
can  be  right.  In  order  to  make  this  antithesis  quite  clear,  it  is  necessary 
to  state  what  is  meant  by  this  conventional  term  "  inflammation  "; 
which  is  used  as  a  cloak  for  a  complex  of  diverse  processes,  as  to  which 
there  is  to-day  even  less  agreement  among  pathologists  than  formerly, 
when  there  never  was  unanimity. 

The  old  conception  of  ';  inflammation,"  which  summed  up  the  mixed 
processes  connoted  by  the  term,  as  the  aggregate  of  its  cardinal  symptoms 
— rubor,  dolor,  color,  and  tumor,  to  which  may  be  added  pyrexia,  is  as 
true  now  as  it  was  in  the  time  of  Celsus  ;  because  it  is  a  mere  description 
of  externals,  and  does  not  concern  itself  with  the  underlying  processes. 

The  most  important  of  these  processes  undoubtedly  is  microbic 
infection  ab  extra  ;  for,  in  the  modern  sense,  there  can  be  no  inflamma- 
tion without  microbes.  In  accordance  with  this,  we  see  that  extensive 
injuries  are  repaired  without  inflammation  when  microbes  are  excluded, 
as  in  simple  fractures  ;  whereas,  when  this  is  not  effected,  the  most 
violent  inflammatory  reaction  ensues,  as  in  compound  fractures.  Thus, 
the  definition  of  inflammation,  as  "  the  succession  of  changes  which 
occurs  in  a  living  tissue  when  it  is  injured,"  is  altogether  inadequate. 
The  changes  which  take  place  in  damaged  structures,  without  the  con- 
currence of  microbes,  by  which  restitutio  ad  integrum  is  effected,  are  -an 
outcome  of  the  reparative  process  ;  and  have  nothing  to  do  with  inflam- 
mation properly  so  called,  although  they  are  often  improperly  included 
within  the  scope  of  this  term.  Hence,  we  must  also  reject  Grawitz' 
definition  of  inflammation,  as  "  the  reaction  of  irritated  and  damaged 
tissues  which  still  retain  their  vitality." 

"  Inflammation  "  being  the  term  originally  applied  to  certain  appear- 
ances met  with  in  mankind,  and  thence  extended  to  similar  appearances 
in  the  higher  animals,  which  are  the  outcome  of  changes  concentring  in 
the  lymph- vascular  system,  it  follows  that  inflammation  in  this  sense, 
can  only  occur  in  organisms  and  tissues  possessing  such  a  system,  and 
capable  of  reacting  to  foreign  microbes  in  this  particular  way.  In  short, 
inflammation  is,  as  Cohnheim  says,  a  particular  kind  of  disturbance  of 
the  circulation.  Hence,  non-vascular  tissues,  and  organisms  in  which 
the  lymph- vascular  system  is  not  evolved  (as  in  the  lower  forms  of  animal 
life  and  in  all  vegetable  organisms),  are  incapable  of  "  inflammation."  > 
1  "  Surgical  Pathology,"  lecture  xliv. 


272  THE  NATURAL  HISTORY  OF  CANCER 

"  No  inflammation  without  bloodvessels,"  is  quite  as  much  a  truism,  as 
"  no  inflammation  without  microbes  ";  and,  in  both  of  these  fundamentally 
important  respects,  there  is  complete  antithesis  between  growth  and 
inflammation — for  the  inception  of  growth  is  as  independent  of  microbes, 
as  it  is  of  bloodvessels  and  nerves. 

Lately  the  tendency  has  manifested  itself,  chiefly  as  the  outcome  of 
Metchnikoff's  teaching,  to  identify  "  inflammation  "  with  phagocytosis, 
and  even  with  "  chemiotaxis  ";  but  this  would  be  to  substitute  new 
names  for  an  old  process  in  defiance  of  historical  tradition,  which  in  the 
matter  of  names  is  the  paramount  authority. 

Nothing  has  done  more  to  obscure  the  fundamental  antithesis  between 
inflammation  and  tumour  growth,  than  the  failure  of  pathologists  to 
discriminate  between  the  phlogistic  and  the  reparative  processes,  both 
of  these  perfectly  distinct  reactions  being  commonly  included  under  the 
term  "  inflammation." 

This  is  specially  noticeable  in  the  condition  called  "  chronic  inflamma- 
tion," which  in  my  opinion  is  not  inflammation  at  all ;  but  an  abnormality 
of  growth,  the  outcome  of  imperfectly  co-ordinated  reparative  efforts. 
Hence,  it  would  be  well  if  the  term  "  chronic  inflammation  "  were  alto- 
gether abolished  from  modern  pathology,  as  being  essentially  mis- 
leading. 

This  confusion  between  "  chronic  inflammation  "  and  the  overgrowth 
marking  imperfect  repair,  is  the  fundamental  misconception  which  under- 
lies and  vitiates  ab  initio  the  Broussaisian  doctrine  of  tumour  formation, 
the  fallaciousness  of  which  I  have  now  sufficiently  laid  bare. 


Precancerous   Conditions. 

It  is  an  ancient  belief,  that  cancer  usually  starts  in  a  part  of  the 
body,  which  has  undergone  antecedent  "  inflammation,"  or  some  other 
departure  from  the  normal ;  rather  than  in  a  part  quite  free  from  any 
such  aberration. 

As  I  have  indicated  in  a  previous  chapter,1  the  proneness  to  originate 
cancer  manifested  by  such  pre-natal  blemishes  as  "  rests,"  moles,  nsevi, 
and  other  developmental  irregularities,  shows  that  there  is  such  a  thing 
as  congenital  local  predisposition  to  the  disease  ;  and  in  this  respect 
there  is  thus  some  warrant  for  the  ancient  belief. 

Moreover,  I  am  persuaded  that  well-ascertained  facts  indicate,  that 
repeated  irritations  of  long  duration  and  moderate  intensity  are,  in  a 
certain  proportion  of  cases,  the  precursors  of  malignant  disease.  Further, 
I  am  convinced  that  parts  thus  chronically  irritated,  may  thereby  be 
rendered  more  apt  to  take  on  neoplastic  action,  than  they  otherwise 
would  have  been.  In  short,  there  is  such  a  thing  as  acquired  local  pre- 
disposition to  cancer.  Thus  may  we  account  for  the  relative  frequency, 
with  which  certain  cutaneous  cancers  are  met  with  in  chimney-sweeps, 
and  other  workers  in  irritant  substances,  such  as  tar,  paraffin  etc.  Here 
also  belong  the  various  "  eczema  cancers,"  "  lupus  cancers,"  "  scar 
cancers,"  "x-ray  cancers"  etc. 

1  Chapter  VII. 


INFLAM:\IATION,  TRAUMA,  AND  OTHER  FACTORS     273 

The  Broussaisians,  however,  are  not  satisfied  to  stop  here  ;  for,  from 
such  considerations  as  the  foregoing,  they  draw  the  unwarrantable  con- 
clusion ;  that  chronic  inflammatory  lesions  are  the  necessary  antecedents 
of  cancer.  It  is  against  this  doctrine  that  I  protest  ;  and  I  will  now 
proceed  to  show  its  erroneousness. 

The  only  evidence  of  any  scientific  value  hitherto  adduced  in  favour 
of  the  Broussaisian  doctrine  of  cancer  causation,  is  to  be  found  in  Volk- 
mann's  *  well-known  analysis  of  223  cases  of  primary  cutaneous  cancer 
of  the  extremities.  In  this  connexion,  it  must  be  borne  in  mind,  that 
although  the  extremities  suffer  more  from  all  kinds  of  traumata,  scars, 
burns,  chronic  ulcers  etc.,  than  any  other  parts  of  the  body,  they  never- 
theless very  seldom  originate  cancer.  Of  7,297  consecutive  primary 
cancers  analysed  by  me,  only  99,  or  1-3  per  cent.,  originated  from  the 
extremities  ;  and  of  these,  72  started  from  the  lower  and  27  from  the 
upper. 

Xow,  Volkmann  found  that  in  no  less  than  88  per  cent,  of  his  cases, 
the  cancerous  disease  had  originated  in  connexion  with  some  pre-existing 
lesion  of  the  part  ;  in  only  12  per  cent,  did  it  appear  to  have  sprung  up 
spontaneously.  If  the  state  of  things  revealed  by  this  analysis,  were 
really  representative  of  the  ordinary  mode  of  development  of  cancer, 
these  data  would  be  strong  evidence  in  favour  of  the  influence  of 
irritation.  But  I  maintain  that  it  is  not  so.  The  cases  analysed 
by  Volkmann  were  not  consecutive  cases,  but  most  of  them  had 
been  recorded  at  various  times  by  different  observers,  with  the  special 
object  of  showing  the  association  between  cancer  and  pre-existing 
local  disease,  as  to  the  occasional  occurrence  of  which  there  is  no 
doubt. 

The  fallacy  of  accepting  these  data,  as  typical  of  what  takes  place  in 
the  ordinary  development  of  cutaneous  cancer,  is  well  seen  by  comparing 
Volkmann's  results  with  the  following  analysis  of  40  consecutively 
occurring  cases  of  primary  cutaneous  cancer  recorded  by  myself,2  in  which 
special  attention  was  directed  to  the  question  of  pre-existing  disease  of 
the  part.  Of  these  40  cases,  only  1  1,  or  27-5  per  cent.,  were  associated  with 
pre-existing  lesions  —  viz.,  old  scars  in  4  cases,  congenital  lesions  in  2  ; 
suppurating  sebaceous  cyst,  soot  wart,  wart  of  eighteen  years'  duration, 
recent  wound,  and  chronic  sinus,  each  in  1  case.  In  other  words,  the 
most  careful  examination,  directed  expressly  to  this  end,  failed  to  reveal 
the  existence  of  any  obvious  pre-existing  local  disease,  in  72  per  cent. 
of  all  cases.  In  like  manner,  of  669  tumours  analysed  ad  hoc  by  Rappok,3 
32  per  cent,  started  from  some  pre-existing  lesion  ;  and,  in  68  per  cent.,  ' 
nothing  of  the  kind  was  noticeable. 

By  careful  inquiries  as  to  the  association  of  the  onset  of  cancer  with 
pre-existing  local  disease,  in  other  parts  of  the  body,  I  have  ascertained 
that,  for  these  localities  also,  the  foregoing  conclusions  are  equally 
valid. 

1  Samml.  klin.  Vortrdge,  1889,  Nos.  334  and  335. 

2  Middlesex  Hospital  Surgical  Reports,  1882  to  1889. 
*  Deutsche  Zeits.  f.  Chir.,  Bd.  xxx.,  S.  465. 


18 


274  THE  NATURAL  HISTORY  OF  CANCER 


In  the  Female  Breast. 

Thus,  with  regard  to  the  female  breast,  it  is  often  asserted  that  cancers 
of  this  part,  are  due  to  antecedent  attacks  of  inflammation  or  abscess, 
yet  no  conclusive  evidence  of  this  has  ever  been  adduced.  Equally 
destitute  of  support  is  the  constantly  reiterated  assertion,  that  the  latter 
lesions  are  of  more  frequent  occurrence  in  the  cancerous,  than  in  the 
non-cancerous. 

The  following  facts  are  conclusive  in  this  respect. 

Winckel l  has  estimated  that  after  1,000  consecutive  accouchements, 
mastitis  developed  in  6  per  cent.  This,  of  course,  refers  only  to  its 
frequency  after  single  deliveries  in  a  succession  of  women  ;  and  not  to 
the  frequency  of  its  occurrence,  in  regard  to  the  total  pregnancies  of 
each  woman,  during  her  entire  puerperal  life.  To  obtain  the  latter 
datum,  Winckel's  percentage  must  be  multiplied  by  4-6,  this  being  the 
average  number  of  accouchements  of  each  married  woman.  Reckoned 
in  this  way,  it  will  be  found  that  27  •  6  per  cent,  of  all  fertile  married 
women  have  suffered,  at  some  period  or  other  of  their  puerperal  life, 
from  inflammatory  disease  of  the  breast.  In  order  to  ascertain  what 
proportion  of  mammary-cancer  patients  suffer  from  similar  affections,  I 
made  special  inquiries  on  this  subject  in  137  cases.  Of  these,  24,  or 
17-5  per  cent.,  gave  a  history  of  some  previous  disease  of  the  breast — 
abscess  in  15,  sore  nipple  in  8,  and  inflammation  in  1  ;  and  in  6  of  these 
cases  the  nipples  were  congenitally  malformed. 

The  above  facts  prove,  that  cancer  patients  are  less  prone  to  inflam- 
matory diseases  of  the  breast,  than  the  non-cancerous. 

Hence,  the  only  basis  for  this  alleged  causation  is,  that  in  a  certain 
proportion  of  cancer  cases,  inflammatory  lesions  have  pre-existed. 
Moreover,  against  the  assumed  setiological  importance  of  previous  inflam- 
matory disease  is  the  fact,  that  in  most  of  the  cases,  the  interval  between 
the  antecedent  disease,  and  the  subsequent  outbreak  of  cancer,  extended 
over  many  years  ;  and,  during  this  period,  the  breast  appeared  to  be 
free  from  any  lesion.  Of  like  import  is  the  fact,  that  cancer  of  the 
breast  is  relatively  almost  as  frequent  in  the  single  and  sterile  as  in  the 
married,  although  the  former  are  much  less  prone  to  inflammatory 
affections  of  the  breast  than  the  latter. 

On  a  priori  grounds,  no  inflammatory  lesion  seems  more  likely  to  be 
the  precursor  of  cancer,  than  chronic  mastitis  ;  and;  since  this  disease 
gives  rise  to  circumscribed  induration,  its  presence  can  hardly  be  over- 
looked. 

Yet  how  rarely  does  mammary  cancer  ever  appear  to  start  in  con- 
nexion with  such  indurations  ?  I  have  met  with  this  conjunction  only 
twice,  in  137  cases  ; 2  hence  it  seems  to  me  improbable  that  chronic 
mastitis  plays  an  important  part  in  the  genesis  of  mammary  cancer. 

1  Path.  u.  Therap.  des  Wochenb.,  1878. 

2  According  to  Gross,  cancer  of  the  breast  appeared  to  develop  out  of  chronic  inflam- 
matory induration  in  49  out  of  907  cases,  or  in  5'4  per  cent.     (International  Journal  of 
Medical  Science,  March,  1888,  p.  222). 


INFLAMMATION,  TRAUMA,  AND  OTHER  FACTORS       275 


In  the  Uterus. 

Similarly,  with  regard  to  uterine  cancer,  it  is  alleged  by  Emmet  and 
his  followers,  that  the  disease  is  almost  invariably  caused  by  child- 
bearing,  lacerations,  "  endometritis,"  or  some  of  the  other  maladies 
incidental  to  the  married  state  ;  while  others  attach  great  importance 
to  catamenial  derangements,  the  abuse  of  venereal  pleasures,  syphilis 
and  gonorrhoea. 

As  I  have  previously  mentioned,  cancer  is  a  disease  of  persons  whose 
previous  life  has  been  healthy,  and  whose  nutritive  vigour  seems  to  promise 
long  life.  It  accords  with  this,  that  the  natural  functions  of  cancer 
patients  are  almost  invariably  performed  with  ease  and  regularity.  Thus, 
in  women  with  uterine  cancer,  the  normality  of  the  catamenial  function 
is  seldom  disturbed  ;  and,  that  it  is  established  earlier  and  ceases  later 
than  in  the  generality  of  women,  is  an  indication  of  vigorous  sexual 
health. 

Just  so  is  it  with  regard  to  marriage,  for  a  much  greater  proportion 
of  uterine-cancer  patients  have  been  married,  than  of  the  female  popula- 
tion of  corresponding  age. 

Of  156  women  with  uterine  cancer,  under  my  observation,  146  (93-2 
per  cent.)  had  been  married,  and  only  10  (6-8  per  cent.)  were  single  ; 
similarly,  of  168  cases  tabulated  by  West  and  Duncan,  only  3  were  single  ; 
thus,  of  these  344  uterine-cancer  patients,  311  had  been  married,  or 
96  per  cent.  ;  and  only  13  were  single,  or  4  per  cent.  In  the  general 
population  only  79  per  cent,  of  women  over  24  ever  marry. 

Of  similar  import  is  the  great  fertility  of  these  cancer  patients. 

Of  143  uterine-cancer  patients  under  my  observation,  only  6  were 
barren  (4-2  per  cent.)  ;  of  528  patients  under  treatment  at  the  Berlin 
Charite  Hospital  (1883-1893)  28  were  barren  (5-3  per  cent.)  :  thus  of  these 
671  patients  34  were  barren,  or  5  per  cent.  Among  married  women  in 
the  general  community,  the  amount  of  sterility  is  much  more  than  this  ; 
it  has  been  estimated  by  Simpson  at  11-6  per  cent. 

The  137  fruitful  women  in  my  list,  averaged  5-6  children  and  0-9  mis- 
carriage each — the  maximum  progeny  being  13  children  and  4  mis- 
carriages (of  which  there  were  2  instances). 

With  regard  to  one-child  sterility,  there  were  10  instances  of  it,  or 
1  in  13-7  ;  which  is  almost  identical  with  the  ratio  found  by  Ansell  to 
prevail  among  fertile  married  women  of  the  general  population. 

To  sum  up,  143  married  uterine-cancer  patients  had  between  them 
767  children  and  123  miscarriages,  the  average  being  5-3  children  and 
0-8  miscarriage  each. 

This  amount  of  fertility  exceeds  that  prevalent  in  the  general  com- 
munity, which  averages  about  4-6  children  and  1  miscarriage  per  mar- 
riage ;  when  allowance  has  been  made  for  the  fact  that  a  considerable 
proportion  of  uterine  cancer  patients  die,  before  the  completion  of  their 
reproductive  life,  it  is  obvious  that  their  fecundity  is  even  higher  than 
from  the  foregoing  figures  it  appears  to  be. 

The  mean  age  at  first  marriage  (in  63  cases)  was  21-6  years  ;  and  the 

18—2 


276  THE  NATURAL  HISTORY  OF  CANCER 

mean  age  at  which  child-bearing  commenced  (in  100  cases)  was  21-8 
years  ;  both  of  these  averages  are  considerably  earlier  than  the  corre- 
sponding figures  for  married  women  of  the  general  community  ;  and  they 
furnish  another  indication  of  the  reproductive  energy  of  these  patients. 

It  will  be  gathered  from  what  has  been  stated,  that  uterine  cancer  is 
of  more  frequent  occurrence  in  the  married,  and  in  those  who  have 
borne  children,  than  in  the  single  and  sterile.  Must  we  infer  from  this, 
that  frequent  parturition  favours  the  development  of  the  disease  ? 
Certainly  no  such  inference  is  warranted  ;  for,  as  the  following  data 
show,  female  cancer  patients  in  general,  manifest  a  similar  high  degree 
of  fertility. 

Thus,  15  women  with  cancer  of  the  rectum,  averaged  6-3  children, 
and  0-7  miscarriage  each  ;  98  breast-cancer  patients  averaged  3-4  children 
and  1-1  miscarriages  each  ;  6  women  with  ovarian  cancer,  averaged  8-2 
children  each  ;  7  rodent-ulcer  patients  averaged  6-8  children  and  2  mis- 
carriages each  ;  and  9  women  with  cancer  of  the  tongue  averaged  4 
children  and  1  miscarriage  each. 

It  is  evident,  therefore,  that  the  high  degree  of  procreative  capacity, 
manifested  by  these  females,  is  merely  one  of  the  consequences  of  that 
exuberant  general  health  and  nutritive  vigour  ;  which,  as  I  have  previously 
mentioned,  is  a  peculiarity  of  cancer  patients. 

It  may  be  inferred,  from  the  fact  that  10  of  the  156  uterine-cancer 
patients  of  my  list,  were  unmarried,  and  all  save  one  childless,  that 
virginity  is  no  safeguard  against  the  disease ;  and,  if  this  evidence  as  to 
virginity  be  deemed  insufficient,  reference  may  be  made  to  many  pub- 
lished cases  in  which  the  presence  of  uterine  cancer  has  been  demon- 
strated, in  women  who  presented  all  the  anatomical  signs  of  virginity. 

I  have  ascertained  that  in  the  great  majority  of  uterine-cancer  cases, 
the  disease  does  not  begin,  until  many  years  after  the  final  cessation  of 
child-bearing.  Of  32  prolific  women  thus  affected,  interrogated  by  me, 
in  28  (87-5  per  cent.)  the  disease  did  not  begin  until  a  year  or  more  after 
the  cessation  of  child-bearing,  the  average  interval  between  the  cessation 
of  child-bearing  and  the  onset  of  the  disease,  in  these  cases,  being  no 
less  than  12-3  years. 

Only  rarely  does  cancer  of  the  uterus  arise  during  pregnancy  (6  in 
97  cases,  or  6-2  per  cent.)  ;  and  within  a  year  after  parturition  its  occur- 
rence is  equally  rare  (6  in  97  cases). 

These  facts  corroborate  my  contention,  as  to  the  independence  of  the 
outbreak  of  the  disease,  of  the  incidents  of  the  reproductive  life. 

Here  it  must  be  mentioned,  that  the  subjects  of  cancer  of  the  corpus 
uteri  are  much  less  prolific,  than  those  with  cervical  cancer. 

Of  31  cases  of  this  kind  tabulated  by  Pichot,  Ruge  "and  Veit,  14 
(45  per  cent.)  were  absolutely  sterile  and  3  had  only  1  miscarriage  each  ; 
while  the  remaining  14  had  between  them  57  children  :  thus,  of  these 
31  women,  the  average  progeny  was  only  1-7  children  each.  When  we 
recollect  the  comparatively  late  age  at  which  this  form  of  the  disease 
supervenes,  the  significance  of  these  figures  is  enhanced. 

As  I  have  previously  pointed  out,  the  ensemble  of  facts  relating  to 
the  life-history  of  the  subjects  of  uterine  cancer  shows,  that  they  have 


INFLAMMATION,  TRAUMA,  AND  OTHER  FACTORS       277 

almost  invariably  led  regular,  sober,  and  industrious  lives.  Personsjof 
drunken  and  dissolute  habits  are  comparatively  seldom  affected.  Of 
160  uterine-cancer  patients  consecutively  under  my  observation,  not  a 
single  one,  so  far  as  I  could  ascertain,  had  ever  been  addicted  to  prostitu- 
tion ;  and,  what  is  still  more  remarkable,  only  one  presented  undoubted 
signs  of  having  had  syphilis. 

In  this  connexion,  the  almost  complete  immunity  of  uterine-cancer 
patients  from  chronic  ulcer  of  the  leg,  is  worth  noting  ;  among  my  cases 
there  was  not  a  single  instance  of  it. 

According  to  Glatter,  of  365  Vienna  uterine-cancer  patients,  91  (nearly 
25  per  cent.)  had  been  prostitutes  ;  but,  it  must  be  remembered,  that  he 
arrived  at  this  conclusion  in  a  rather  peculiar  way — viz.,  by  assuming 
that  all  those  described  in  the  registers  as  "  Handarbeiterinnen,"  were — 
as  a  matter  of  course — "  Lustdirne,"  which  seems  to  be  an  unwarrantable 
assumption.  At  any  rate,  my  experience  in  this  respect  is  diametrically 
opposed  to  Glatter's  conclusion  ;  and  in  this  I  am  in  accord  with  Ducha- 
telet,  Lebert,  Walshe,  Winckel,  Tanner  and  Schroeder.  The  high 
fecundity  of  uterine-cancer  patients  strongly  favours  my  views  ;  for,  a 
large  proportion  of  prostitutes  are  sterile,  or  relatively  infertile. 

Martin,  Bruns  and  others,  think  that  previous  attacks  of  gonorrhoea, 
predispose  cancer  of  the  uterus  ;  but  they  have  adduced  no  convincing 
arguments  in  support  of  this  theory,  which  is  at  variance  with  all  the 
information  at  my  disposal. 

With  regard  to  the  influence  of  lacerations — which  may  be  associated 
with  sub-involution,  endometritis,  hyperplasia,  erosions,  polypi  etc. — 
in  the  causation  of  uterine  cancer,  some  gynaecologists  have  gone  so  far 
as  to  assert,  that  the  disease  always  or  frequently  originates  in  them. 

In  order  to  show  the  fallacy  of  this  view,  it  is  necessary  to  bear  in 
mind  the  following  facts  about  lacerations.  They  are  usually  confined 
to  the  inferior  segment  gf  the  uterus  ;  and  at  first  labours  they  are  of 
such  frequent  occurrence,  as  to  be  regarded  by  many  gynaecologists  as 
inevitable.  Injuries  of  this  kind  are  almost  always  multiple  ;  and  in 
the  majority  of  cases  the  lesion  is  bilateral,  being  most  marked  on  the 
left  side,  opposite  the  situation  usually  occupied  by  the  foetal  occiput. 
In  extent  and  depth  they  are  variable,  but  in  most  cases  the  injury  is 
only  slight.  The  worst  tears  are  met  with  after  very  rapid,  tedious  and 
instrumental  labours.  The  occurrence  of  congenital  cervical  fissures, 
very  like  the  traumatic  ones,  and  in  precisely  similar  situations,  has 
been  demonstrated  by  Fischel ;  and  it  is  probable  that  the  latter  are 
often  confused  with  congenital  flaws  of  this  kind. 

Emmet  and  Ms  followers  regard  lacerations  as  a  veritable  Pandora's 
box  of  uterine  maladies  ;  in  fact,  the  number  of  diseases  they  ascribe  to 
this  source,  wellnigh  exhausts  the  list.  With  regard  to  cancer,  they 
even  go  so  far  as  to  assert,  that  in  all  cases  the  disease  originates  in 
lacerations. 

The  only  evidence  adducible  on  behalf  of  these  extreme  views  is  the 
great  frequency  of  lacerations  ;  which,  of  itself,  is  of  course  quite  insuffi- 
cient, even  when  the  two  morbid  conditions  coexist.  In  cases  of  this 
kind,  carefully  observed  by  John  Williams,  in  not  a  single  instance 


278  THE  NATURAL  HISTORY  OF  CANCER 

did  the  cancerous  disease  appear  to  have  started  from  the  lacera- 
tion. 

Against  any  such  theory  it  may  further  be  objected  ;  that  if  uterine 
cancer  really  originated  in  lacerations,  it  would — like  the  latter — nearly 
always  be  multiple,  and  its  precise  seats  of  origin  would  correspond  with 
the  localities  in  which  lacerations  usuaUy  occur  ;  but,  in  the  initial  mani- 
festation of  the  disease,  none  of  these  conditions  are  fulfilled. 

Moreover,  against  the  assumed  setiological  importance  of  lacerations, 
is  the  fact ;  that  the  interval  between  the  laceration  and  the  outbreak 
of  cancer,  extends  over  many  years,  and  during  this  long  period  the 
uterus  appears  to  be  free  from  disease. 

Thus,  the  average  age  at  which  child-bearing  commenced  in  my  cases 
was  21-8  years  ;  whereas  in  the  same  women  the  average  age  at  which 
uterine  cancer  supervened  was  forty-four  years  :  thus,  between  the  out- 
break of  the  disease  and  its  alleged  causation,  a  period  of  no  less  than 
,22-2  years  intervened. 

Of  like  significance,  as  previously  mentioned,  is  the  long  interval 
usually  found  between  the  cessation  of  child-bearing  and  the  onset  of 
cancer. 

Another  indication  pointing  in  the  same  direction,  is  furnished  by 
the  fact,  that  rapid,  tedious  and  instrumental  labours — after  which 
lacerations  are  commonest  and  most  severe — are  relatively  rare  in  uterine- 
cancer  patients. 

Of  65  cases  in  my  list,  in  which  the  character  of  the  labours  was 
noted  ;  in  59  they  were  natural  (tedious  or  difficult  in  9),  and  in  only  6 
were  they  instrumental. 

Thus,  notwithstanding  many  allegations  to  the  contrary,  no  reliable 
evidence  has  hitherto  been  adduced,  of  any  connexion  between  antecedent 
morbid  affections  of  the  uterus  and  cancer. 

The  great  majority  of  the  patients  under  my  observation,  had  been 
remarkably  free  from  previous  uterine  disease  of  any  kind. 

Of  137  cases  in  which  special  inquiries  were  made,  only  13  had  suffered 
from  previous  disease  of  the  uterus  ;  viz.,  leucorrhoea  7,  prolapse  3,  and 
endometritis  3. 

This  is  in  entire  agreement  with  the  facts  previously  mentioned,  as 
to  the  good  catamenial  health  of  these  patients,  their  remarkable  fertility 
when  married,  and  the  ensemble  of  their  life-history. 

Since  this  was  written,  it  has  been  pointed  out  to  me  that  West l  had 
previously  come  to  the  same  conclusion  ;  thus  he  says  :  "It  may  be 
supposed  that  we  shall  find  indications  of  previous  uterine  disorder  (as 
some  suppose  of  uterine  inflammation),  out  of  which  cancerous  disease 
has  been  subsequently  developed.  Evidence,  however,  seems  to  be 
directly  opposed  to  this  supposition  ;  for,  in  the  history  of  only  5  out  of 
the  whole  170  uterine-cancer  cases,  is  there  any  mention  of  previous 
uterine  ailment." 

The  great  rarity  of  cancer  of  the  procident  uterus  is  a  fact  of  like 
import.  Schmidt  2  reports  that  of  294  cases  of  cancer  of  the  uterus 
under  treatment  at  the  Halle  Clinic,  only  2  were  associated  with  pro- 
1  "  Diseases  of  Women,"  1864,  p.  365.  2  Monats.  f.  Geb.  u.  Gyn.,  Bd.  vii.,  Heft.  5. 


INFLAMMATION,  TRAUMA,  AND  OTHER  FACTORS       279 

lapse  ;  and  of  423  women  admitted  for  prolapse,  only  2  were  found  to 
have  cancer  as  well. 

These  facts  were  well  known  to  the  great  Cruveilhier,1  who  perti- 
nently remarks  :  "  On  doit  s'etonner  que  le  col  uterin  qui  est  si  sou  vent 
le  siege  de  degeneration  cancereuse,  alors  qu'il  occupe  sa  situation  nor- 
male,  devienne  si  rarement  malade  dans  le  cas  de  prolapsus." 

Of  similar  import  is  the  great  rarity  of  cancer  arising  from  uterine 
polypoid  pseudo-plasms,  of  which  comparatively  very  few  cases  have 
been  recorded. 

Gastric  Ulcer  and  Gastric  Cancer. 

It  is  claimed  by  some  practitioners,  that  most  cases  of  gastric  cancer 
originate  from  local  ulceration.  Thus,  according  to  Mayo  Robson,2 
"  Every  cancer,  whether  external  or  internal,  follows  on  a  pre-cancerous 
condition,  such  as  cancer  of  the  gall-bladder  on  ulceration  produced  by 
gall-stones,  cancer  of  the  stomach  on  chronic  gastric  ulcer,  epithelioma 
of  the  penis  on  irritation  under  a  phimosis  etc."  I  propose  to  show  that 
these  conclusions  are  untenable,  being  completely  at  variance  with  well- 
ascertained  facts. 

Gastric  cancer  and  gastric  ulcer  are  such  comparatively  common 
diseases,  that  their  not  infrequent  concomitance  cannot  be  accepted  as 
presumptive  evidence  of  setiological  relationship. 

The  probability  of  any  such  causative  connexion  existing  between 
the  two  maladies  is  contra-indicated,  among  other  considerations,  by  their 
diversity  in  localization. 

Thus,  cancer  of  the  stomach,  so  frequently  originates  at  the  pylorus, 
that  it  is  commonly  spoken  of  as  pyloric  cancer  ;  analysis  of  4,574  cases  of 
gastric  cancer  (Brinton,  Welch,  Gurlt,  Habershon,  Luton  and  Fenwick), 
shows  that  in  no  less  than  2,724  of  these  cases,  or  nearly  60  per  cent., 
the  disease  was  thus  located.  On  the  other  hand,  Welch's  3  analysis  of 
793  cases  of  gastric  ulcer,  shows  that  only  95 — or  12  per  cent. — were 
pyloric  in  situation. 

.  According  to  these  data  then,  the  great  majority  of  all  pyloric  cancers 
arise  in  a  situation,  where  local  ulcers  are  of  great  rarity  ;  and,  conse- 
quently, they  must  usually  be  quite  independent  of  any  such  antecedent 
lesion. 

Moreover,  the  commonest  seat  of  gastric  ulcer  is  the  lesser  curvature — 
where  288  (36-3  per  cent.)  of  Welch's  793  cases  were  located — which  is  a 
rare  situation  for  cancer,  only  12-2  per  cent,  of  Brinton  and  Welch's 
numerous  cases,  originating  there. 

In  like  manner,  the  duodenum  is  frequently  the  seat  of  ulceration,  of 
similar  nature  to  that  met  with  in  the  stomach,  indeed,  both  of  these 
localities  are  not  infrequently  concomitantly  affected ;  yet,  cancer  of  the 
duodenum  is  one  of  the  very  rarest  diseases  :  for  of  7,297  primary  malig- 
nant epithelial  tumours  tabulated  by  me,  consecutively  under  treatment 
at  several  of  the  chief  London  hospitals,  comprising  499  intestinal  cancers, 
only  4  originated  in  the  duodenum ;  similarly,  of  1,148  intestinal 

1   Anat.  Path.,  liv.,  xvi.  *  Lancet,  1904,  vol.  ii.,  p.  1547. 

3  Pepper's  "  System  of  Medicine  "  (art.  "  Gastric  Ulcer  "). 


280  THE  NATURAL  HISTORY  OF  CANCER 

cancers,  Ewald  found  that  only  19  originated  in  the  duodenum,  and  other 
statistical  data  are  to  the  same  effect.1 

Another  item  pointing  in  the  same  direction,  is  the  diverse  sex  inci- 
dence of  the  two  maladies  ;  thus,  while  cancer  of  the  stomach  is  of  much 
greater  relative  frequency  in  males  than  in  females,  the  female  liability 
to  gastric  ulcer  is  largely  in  excess  of  that  of  males. 

In  illustration  of  this,  the  following  data  are  conclusive  :  the  Registrar  - 
General's  Sixty-first  Annual  Report  shows  that  21-4  per  cent,  of  the  cancer 
mortality  among  males  was  due  to  gastric  cancer,  the  corresponding  figure 
for  females  being  13-2  per  cent.  ;  with  regard  to  gastric  ulcer,  of  177  con- 
secutive cases  tabulated  by  me  2 — as  occurring  among  32.505  male  and 
28,175  female  in-patients  in  London  hospitals — 117  were  females,,and  60 
were  males,  showing  that  the  liability  of  the  former  is  more  than  double 
that  of  the  latter  ;  and  data  collected  by  others  are  of  similar  import 
(Welch,  Saundby,  Bulstrode  etc.).  According  to  Saundby,3  on  the  basis 
of  clinical  data,  women  are  twenty  times  as  prone  to  gastric  ulcer  as  men  ; 
and  Bulstrode  reports,  that  of  500  cases — admitted  into  the  London 
hospital,  1897  to  1902 — 402  were  women  and  only  98  men. 

The  age  incidence  of  the  two  maladies  is  also  very  different,  half  of  all 
gastric  ulcers  being  met  with  between  the  ages  of  20  and  30,  and  almost 
the  whole  of  them  being  comprised  between  the  years  18  to  38  ;  whereas 
comparatively  few  gastric  cancers  are  met  with  before  40,  the  average  age 
at  onset  being  51  for  males  and  40-5  for  females,  most  cases  being  com- 
prised in  the  decennium  50  to  60. 

Finally,  it  may  be  mentioned  that  the  clinical  symptoms  associated 
with  gastric  cancer,  are  seldom  indicative  of  antecedent  ulceration  ;  for, 
cancer  of  the  stomach  runs  a  rapidly  fatal  course,  the  average  duration  of 
the  symptoms  seldom  exceeding  fifteen  months. 

The  cumulative  weight  of  these  diverse  indications  against  there 
being,  as  a  rule,  any  aetiological  connexion  between  gastric  ulcer  and 
gastric  cancer,  is  so  overwhelming,  as  to  be  practically  conclusive; 
although  of  course,  I  do  not  mean  to  deny  that  cancer  may  exceptionally 
originate  from  gastric  ulcer. 


Gall-stones  and  Cancer  of  the  Gall-bladder. 

The  very  frequent  association  of  gall-stones,  with  that  rare  disease, 
cancer  of  the  gall-bladder,  has  induced  many  practitioners  to  assume  a 
causative  relation  of  the  former  to  the  latter  ;  and,  in  reference  to  this 
presumption,  Mayo  Robson  says  :  "  The  preventive  treatment  for 
cancer  of  the  gall-bladder  is  obviously,  removal  of  the  source  of  irrita- 
tion." This  conclusion  seems  to  me  without  scientific  warrant.  To  give 
it  even  some  air  of  probability,  it  would  be  necessary  to  show  that  cancer 

1  Of  42,000  necropsies  at  Vienna  hospitals,  comprising  3,583  cases  of  cancer,  of  which 
443  were  intestinal,  only  7  originated  in  the  duodenum  (Schlesinger,  Wien.  klin.  Woch., 
1898,  Xr.  10,  p.  245).  Eighteen  thousand  necropsies  at  Guy's  Hospital  revealed  only  10 
cases  of  primary  malignant  disease  of  the  duodenum — 6  sarcoma,  4  epithelioma  (Perry 
and  Shaw,  Guy's  Hospital  Reports,  1894,  vol.  1.,  p.  214). 
"  Influence  of  Sex  in  Disease,"  London.  1885,  p.  28. 

3  British  Medical  Journal,  1900,  vol.  i.,  p.  121. 


INFLAMMATION,  TRAUMA,  AND  OTHER  FACTORS      281 

of  the  gall-bladder  is  of  fairly  common  occurrence  ;  whereas,  in  reality,  it 
is  one  of  the  very  rarest  cancerous  manifestations  :  thus  of  7,297  1  cancer 
patients,  under  treatment  in  large  London  hospitals,  I  found  that  only  1 1 
had  primary  cancer  of  the  gall-bladder  ;  Gurlt,2  in  Vienna  hospitals,  X 
reported  only  5  instances  in  11,131  cancer  patients  ;  and  Reiche,3  from 
the  mortality  statistics  of  Hamburg,  48  cases  (9  males,  and  39  females) 
in  12,484  cancer  deaths. 

Moreover,  of  115  necropsies  on  persons  with  gall-stones,  Mosher4 
found  only  2  affected  .with  cancer  of  the  gall-bladder. 

In  the  face  of  these  facts,  it  is  surprising  to  find  such  a  conscientious 
author  as  Rolleston,5  stating  that  primary  cancer  of  the  gall-bladder  "  is 
by  no  means  a  rare  disease,"  without  adducing  any  evidence  in  support 
thereof. 

In  like  manner  Robson  says  :  "  This  disease  is  not  nearly  so  uncommon 
as  was  formerly  believed  "  ;  but,  in  support  of  this  pious  opinion,  not  one 
jot  or  tittle  of  evidence  is  adduced. 

The  great  rarity  of  primary  cancer  of  the  gall-bladder,  is  thus  shown 
to  be  an  indubitable  and  incontrovertible  fact.  On  the  other  hand,  gall- 
stones are  of  frequent  occurrence  in  the  general  community,  Kehr  and 
others  having  found  them  in  about  10  per  cent,  of  all  adults,  as  deter- 
mined by  post-mortem  examination.  It  follows  from  these  considera- 
tions, that  gall-stones  can  very  rarely  be  the  cause  of  primary  cancer  of 
the  gall-bladder,  even  if  we  suppose — which  is  most  unlikely  in  view  of 
Mosher's  data — that  every  gall-bladder  cancer  is  caused  in  this  way. 

As  I  have  elsewhere  pointed  out,6  cancerous  patients  in  general  are 
more  prone  to  gall-stones,  than  are  the  non-cancerous  of  the  same  age 
and  sex  in  the  community  at  large  ;  and  Colwell 7  has  recently  estimated 
that  the  cancerous  are  two  and  a  half  times  as  prone  to  gall-stones  as  the 
non-cancerous,  irrespective  of  the  seat  of  the  primary  growth. 

I  submit  that  the  foregoing  data  only  admit  of  one  interpretation, 
viz.,  that  cancer  of  the  gall-bladder  is  seldom,  if  ever,  caused  by  the  gall- 
stones so  often  found  associated  with  it. 

In  cases  of  this  kind,  we  must  rather  look  to  antecedent  morbid  con- 
ditions of  the  cystic  mucosa,  as  being  the  determining  factor  of  these 
concretions. 

It  accords  with  this,  that  calculous  concretions  of  the  kidney  and  renal 
pelvis,  which  are  of  common  occurrence,  are  hardly  ever  associated  with 
malignant  disease  of  these  parts. 


Phimosis  and  Cancer  of  the  Penis. 

With  regard  to  the  alleged  causative  connexion  between  cancer  of  the 
penis  and  phimosis,  it  is  to  be  remarked  that  phimosis  is  one  of  the 
commonest  anomalies  ;  and  a  very  large  proportion  of  the  male  population 
is'affected  in  this  way,  often  to  an  extreme  degree. 

1    Vide  Chapter  XVIII.  2  Arch.  f.  klin.  CUr.,  Bd.  xxv.,  S.  420. 

3  Deutsche  mtd.  Woch.,  1900,  Xos.  7  and  8. 

4  Johns  Hopkins  Hospital  Bulletin,  1901,  p.  253. 

6  "  Diseases  of  the  Liver,"  etc.,  1905,  pp.  620  and  627.  a  Chapter  XVI. 

7  Middlesex  Hospital  Archives,  1905,  vol.  v.,  p.  148. 


282  THE  NATURAL  HISTORY  OF  CANCER 

If,  therefore,  as  alleged,  phimosis  is  a  potent  cause  of  cancer  of  the 
penis,  this  particular  local  variety  of  cancer  should  be  very  common. 

But,  the  ascertained  facts  show  that  it  is  far  otherwise  ;  thus,  of  2,669 
men  with  cancer,  under  treatment  in  the  chief  London  hospitals,  I  found 
that  only  106  had  cancer  of  the  penis  ;  and  of  2,891  similar  cases  in  Vienna 
hospitals,  Gurlt  found  only  108  thus  affected  ;  therefore,  rather  less  than 
4  per  cent,  of  these  male  hospital  patients  were  affected  with  this  variety 
of  cancer. 

Englisch's  statistics,1  embracing  a  much  larger  number  of  cases — 
namely  12,607 — show  that  less  than  2  per  cent.  (1-81)  of  all  cancers  in 
men,  affect  the  penis  ;  the  Registrar-General's  Reports  show  that  the 
rarity  of  cancer  of  the  penis  is  much  greater,  than  even  these  hospital  data 
indicate  ;  for,  of  9,685  men  who  died  of  cancer  during  the  year  1900,  only 
100  died  of  cancer  of  the  penis,  or  about  1  per  cent. ;  Reiche's2  Hamburg 
mortality  data  (1872-1898)  show  a  still  smaller  proportion,  viz.,  only 
17  cases  in  4,906  male  cancer  deaths,  or  0-34  per  cent.  ;  while  the  United 
States  Census  Report,  for  1900,  shows  that  this  local  variety  of  disease  is 
even  rarer  in  that  country  ;  since  only  0-18  per  cent,  of  the  male  cancer 
deaths  were  due  to  cancer  of  the  penis. 

The  United  States  negroes  are  said  to  be  more  universally  and  more 
severely  affected  with  phimosis,  than  any  other  race  ;  yet,  for  the  year 
1900 — although  the  cancer  death-rate  of  male  negroes  amounted  to 
28-6  per  100,000  living — not  a  single  death  from  cancer  of  the  penis  was 
recorded  during  the  whole  year.  This  great  rarity  of  cancer  of  the  penis 
in  negroes  is  fully  confirmed  by  Rodman's  3  experience  in  Philadelphia,  by 
the  Louisville  statistics,  and  by  other  independent  testimony. 

Moreover,  it  is  worth  noting,  that  Jews  are  as  little  liable  to  cancer  of 
the  penis  as  non- Jews. 

If  phimosis  were  really  a  potent  cause  of  cancer  of  the  penis,  how  very 
different  all  this  would  be. 


"  Paget's  Disease  "  of  the  Nipple  and  Areola,  and  Cancer  of  the  Breast. 

Attention  was  first  prominently  directed  to  this  subject  by  Paget's 
well-known  essay  on  "  Disease  of  the  Mammary  Areola  preceding  Cancer 
of  the  Mammary  Gland,"  which  was  published  in  1874.4 

He  reported  cases  in  which  initial  lesions  of  this  kind  were,  after 
various  intervals,  followed  by  the  formation  of  cancer  in  the  breast ;  and 
the  conclusion  was  drawn  that  this  sequence  "  very  often  "  happened. 
In  this,  there  can  be  no  doubt,  Paget  was  mistaken.  Indeed,  he  admitted 
that  the  areolar  affection  might  often  be  cured,  without  any  ill  conse- 
quences ensuing  ;  and  Velpeau  had  previously  reported  many  instances  of 
this  kind.  Paget  adduced  no  statistical  data  in  support  of  his  dictum,  as 
to  the  presumed  frequency  of  the  cancerous  sequel,  for  none  were  then 
available. 

1  Allgem.  wiener  vied.  Zeit.,  1902,  No.  16. 

2  Deutsche  med.  Woch.,  1900,  Nos.  7  and  8.  ' 

3  "  International  Text-Book  of  Surgery,"  1900,  vol.  ii.,  p.  734. 

4  St.  Bartholomew's  Hospital  Reports,  vol.  x.,  p.  87. 


INFLAMMATION,  TRAUMA,  AND  OTHER  FACTORS       283 

Since  then,  however,  the  subject  has  been  numerically  investigated  on 
a  large  scale  ;  and  it  has  thereby  been  proved,  that  cancer  of  the  breast 
follows  "  chronic  eczema  "  of  the  nipple  etc.,  in  less  than  1  per  cent,  of  the 
total  cases  :  thus  of  5,440  mammary  cancers  tabulated  by  various  authors,1 
in  only  41  (0-75  per  cent.)  did  the  disease  begin  in  this  way.  Surgeons 
may  therefore  disabuse  their  minds  of  the  idea,  that  "  Paget's  disease  " 
plays  an  important  part  in  the  pathogenesis  of  mammary  cancer.  Areolar 
affections  of  this  kind,  which  are  rare,2  are  only  exceptionally  followed  by 
the  outbreak  of  mammary  cancer  ;  consequently,  the  mamma  should 
never  be  extirpated  for  lesions  of  this  kind,  unless  signs  of  concomitant 
malignant  disease  are  also  present. 


"  Lupous  Cancer." 

Lately  a  great  deal  of  attention  has  been  given  to  this  rare  manifesta- 
tion, which  has  been  cited  as  evidence  of  the  belief,  that  "  inflammation 
may  slide  into  cancer."  With  regard  to  this  suggestion  we  may  at  the 
outset  remark,  that  although  lupus  and  cancer  are  very  common  affections 
and  fairly  often  concomitant,  yet  "lupous  cancer  "  is  certainly  exceedingly 
rare  ;  it  would  be  far  otherwise  if  lupus  had  any  special  proclivity  to 
cancer.  Besides  this,  although  lupus  is  a  disease  which  supervenes  in 
early  life,  cancer  does  not  originate  from  it,  until  the  patient  has  attained 
the  cancer  age  ;  the  most  therefore  that  can  be  legitimately  claimed  for 
lupus,  as  a  factor  in  the  causation  of  cancer,  is  that  it  imparts  local  tissue 
proclivity.  Oftener  than  not,  "  lupous  cancer  "  is  merely  a  "  scar  cancer," 
the  outcome  of  chronic  lesions  determined  by  cicatrization  of  the  local 
disease,  or  of  repeated  injuries  of  the  part  by  operative  procedures.  As 
is  well  known,  in  lupus  and  in  the  scars  resulting  from  its  erasion  etc., 
histological  appearances  which  are  very  "  epithelioma-like,"  are  usual, 
even  in  the  absence  of  all  cancerous  manifestations.  For  further  infor- 
mation relating  to  this  subject,  reference  may  be  made  to  the  publications 
of  J.  Hutchinson,3  Bayha,4  Steinhauser,  Wild  and  others. 


Leucoplasia,  Syphilis  and  Smoking,  in  Relation  to  Lingual  and  Buccal 

Cancer. 

In  many  parts  of  the  body,  such  as  the  oral  cavity,  the  outbreak  of 
cancer  is  fairly  often  preceded  by  obvious  hyperplastic  changes — leuco- 
plasia — of  the  surface  epithelia. 

Of  78  cases  of  lingual  and  buccal  cancer,  examined  ad  hoc  by  me,5 
lesions  of  this  kind  pre-existed  in  18  ;  of  80  similar  cases  by  Butlin,6  in 

1  Bryant,  Gross,  Delbet,  J.  C.  Warren,  Bergmann,  Shield,  H.  Morris,  Campiche  and 
Lazarus- Barlow. 

2  "  Of  15,000  women  examined  at  the  gynaecological  clinic,  Chambers  met  with  only 
two  cases  "  (Transactions  of  the  London  Obstetrical  Society,  1880,  vol.  xxii.,  p.  266). 

3  Archives  of  Surgery,  October,  1890,  p.  138. 

4  Bruns'  Beitr.  z.  klin.  Chir.,  1887. 

6  Middlesex  Hospital  Surgical  Report,  1888,  p.  107. 
6  "Diseases  of  the  Tongue,"  1885,  p.  265. 


284  THE  NATURAL  HISTORY  OF  CANCER 

16  ;  and  of  61  by  H.  Morris,1  in  13  :  thus  of  these  219  cases,  leucoplasia 
pre-existed  in  47,  or  in  about  22  per  cent. 

In  the  great  majority  of  these  cancer  cases,  there  was  no  indication  of 
any  such  antecedent  lesion  ;  hence,  it  may  be  concluded  that  although 
leucoplasia  predisposes  to  cancer,  it  is  by  no  means  a,  necessary  or  even 
usual  antecedent  of  this  malady. 

Leucoplasia,  according  to  Schwimmer,2  is  a  rare  disease  ;  for,  of  5,000 
persons  examined  as  to  its  presence  only  20  were  affected.  It  is  of  much 
more  frequent  occurrence  in  men  than  in  women  ;  for,  of  Neisser's  547 
cases  only  24  were  women. 

Far  too  little  is  as  yet  known  of  the  natural  history  of  leucoplasia,  to 
enable  us  to  say  in  what  proportion  of  cases  it  eventuates  in  cancer  ;  but, 
in  an  able  investigation  into  this  matter  by  the  veteran  Fournier,3  of 
321  tabulated  cases,  97  or  30  per  cent.,  ended  thus.  Of  course,  many 
of  these  patients  came  under  notice  with  the  cancerous  disease  already 
developed ;  so  that  it  is  impossible  to  say,  that  this  percentage  really 
represents  the  natural  outcome  of  leucoplasia,  as  many  slight  cases  would 
probably  never  apply  for  treatment.  Hence  it  may  be  inferred  that 
leucoplasia  only  exceptionally  ends  in  cancer. 

It  accords  with  this  that  leucoplasia  is  usually  a  very  chronic  affection  ; 
and  many  cases  have  been  recorded  of  from  25  to  45  years'  duration, 
without  having  undergone  any  cancerous  change  ;  of  12  instances  of  this 
kind  in  H.  Morris'  list,  in  5  the  duration  of  the  disease  had  exceeded 
.10  years. 

Leucoplasia  originates  at  a  much  earlier  age  than  lingual  cancer,  for 
the  average  age  at  onset  of  H.  Morris'  12  leucoplasia  patients,  was  about 
thirty-nine  years  ;  whereas,  the  average  age  for  the  onset  of  lingual  cancer 
I  have  found  to  be  about  fifty-four  years.  This  accords  with  Barker's  4 
results ;  for,  of  29  cases  in  which  cancer  followed  leucoplasia,  he  found 
that  the  average  interval  was  rather  more  than  14  years. 

It  is  thus  noticeable  that,  even  in  patients  with  leucoplasia,  lingual 
cancer  does  not  supervene  until  about  the  age-period  fifty  to  sixty,  at 
which  it  usually  eventuates  in  persons  free  from  leucoplasia. 

According  to  Fournier,  80  per  cent,  of  324  leucoplasia  patients  had 
been  infected  with  syphilis  ;  while,  in  the  other  20  per  cent,  syphilis  could 
be  excluded. 

Of  88  cases  of  cancer  of  the  tongue  and  mouth,  in  which  I  made  special 
inquiries,  there  was  evidence  of  previous  syphilis  in  31 ;  and  of  H.  Morris' 
58  cases  in  12  :  in  the  other  cases  syphilis  could  be  excluded. 

From  these  figures,  it  is  evident  that  syphilis  plays  a  more  important 
part  in  the  causation  of  leucoplasia,  than  it  does  in  lingual  cancer. 

It  is  the  same  with  tobacco-smoking,  for  this  habit  is  far  more  con- 
ducive to  leucoplasia — "  smoker's  patch  " — than  it  is  to  cancer. 

Thus,  of  247  leucoplasia  patients,  Fournier  found  that  97  per  cent, 
were  smokers  ;  182  of  these  were  syphilitic  subjects,  of  whom  96  per  cent. 

1  Transactions  of  the  Medical  Society,  London,  1884,  vol.  vi. 

2  Transactions    of    the    International    Medical    Congress,   London,   1881,   vol.   iii., 
p.  171. 

3  C.  R.  Internal.  Med.  Cong.,  Paris,  1900. 

4  "  Holmes'  System  of  Surgery,"  1883,  vol.  ii.,  p.  516. 


INFLAMMATION,  TRAUMA,  AND  OTHER  FACTORS       285 

were  smokers  ;  and  of  65  non-syphilitic  subjects,  98-4  per  cent,  were 
smokers. 

Hence,  though  syphilis  or  smoking  alone  may  cause  leucoplasia,  the 
combination  of  the  two  gives  the  greatest  proclivity. 

With  regard  to  the  relation  of  smoking  to  cancer  of  the  tongue  and 
mouth,  special  inquiries  made  by  me  show,  that  of  77  cancer  patients, 
12  had  never  smoked  ;  of  the  others,  41  had  been  great  smokers,  and  24 
moderate  smokers,  while  11  of  the  smokers  had  also  chewed. 

The  women  of  Western  Europe  seldom  smoke,  but  this  does  not  give 
them  exemption  from  cancer  of  the  tongue  and  mouth,  although  they  are 
very  much  less  prone  to  it  than  men. 

I  have  seen  it  stated  that,  but  for  syphilis  and  smoking,  there  would 
be  no  lingual  and  buccal  cancer  ;  such  facts  as  the  foregoing  show  the 
absurdity  of  this  statement.  Besides,  tobacco  smoking  was  unknown  in 
Europe  prior  to  the  discovery  of  America,  while  cancer  of  the  tongue  and 
mouth  was  then  an  old-established  and  well-recognized  disease  ;  and,  with 
regard  to  syphilis  in  its  present  form,  most  of  those  who  have  specially 
studied  the  subject  believe,  that  it  also  came  to  us  from  America.  In 
Finisterre,  where  women  habitually  smoke  short  pipes,  Hertaux  never 
saw  a  single  case  of  oral  cancer,  although  the  disease  is  common  among 
men  ;  and  testimony  to  the  like  effect  comes  from  other  countries,  where 
women  have  long  been  in  the  habit  of  smoking. 

Special  inquiries  made  by  me,  as  to  the  precise  situation  of  the  initial 
outbreak  of  lingual  cancer,  show  that  in  nearly  half  (48  per  cent.)  of  the 
total  cases,  the  edge  of  the  tongue  is  the  part  affected  ;  on  the  other  hand, 
this  is  a  comparatively  rare  site  for  leucoplasia,  which  in  the  great  majority 
of  cases  affects  the  dorsum — a  situation  in  which  lingual  cancer  very  rarely 
originates — only  in  about  5  per  cent,  of  the  total  cases,  according  to  my 
researches. 

Again,  a  common  site  for  leucoplasia  is  the  angle  of  the  mouth  ;  but 
it  is  very  rare  for  cancer  to  develop  in  this  situation. 

From  these  facts  it  may  be  inferred  that,  even  when  leucoplasia  and 
cancer  coexist,  the  latter  disease  often  originates  elsewhere  than  in  the 
leucoplasia  patch.  A  case  reported  by  H.  Morris  x  strikingly  illustrates 
this  feature  ;  his  patient  had  suffered  from  the  papillary  form  of  leuco- 
plasia, affecting  the  dorsum  of  the  tongue,  for  several  years,  when  epi- 
thelial cancer  of  the  lower  lip  supervened.  Moreover,  leucoplasia  has 
been  known  to  develop,  after  the  outbreak  of  cancer,  as  in  cases  reported 
by  Shield  and  Butlin. 

From  the  consideration  of  the  various  items  above  set  forth  it  may  be 
inferred,  that  intrinsic  causes  are  much  more  important  factors  in  the 
origination  of  cancer  than  extrinsic  ones  ;  which  are  by  no  means  its 
necessary  antecedents.  In  the  vast  majority  of  cases,  the  outbreak  of 
this  disease  appears  to  be  entirely  spontaneous  ;  that  is  to  say,  it  cannot 
be  attributed  to  the  immediate  action  of  any  appreciable  extrinsic  cause 
whatever. 

1  Transactions  of  the  Medical  Society,  Ixtndon,  1884,  vol.  vi.  (Case  14  in  Table  III.). 


286  THE  NATURAL  HISTORY  OF  CANCER 

Trauma  and  Cancer. 

Those  who  maintain  that  cancer  is  commonly  caused  by  trauma 
must  explain  how  it  is  that  men,  who  suffer  three  times  as  often  from 
traumata  as  women,  are,  nevertheless,  only  about  half  as  liable  to  cancer. 

Thus,  of  9,229  consecutive  cases  of  trauma  under  treatment  at  four 
large  London  hospitals,  I  have  found  that  6,856  were  males  and  2,372 
females,  or  2-89  males  to  1  female.  Similarly,  of  240,063  deaths  from 
traumata,  tabulated  by  the  Registrar-General  for  the  twenty-five  years 
1848-1872,  178,005  were  males  and  62,058  females,  or  2-8  males  to  1 
female.  On  the  other  hand,  of  7,878  consecutive  cases  of  cancer  under 
treatment  at  the  above-mentioned  hospitals,  2,861  were  males,  and  5,017 
females,  or  1  male  to  1-7  females.  Similarly,  of  the  19,433  cancer  deaths 
in  England  and  Wales  during  1890,  7,137  were  males  and  12,296  females, 
or  1  male  to  1-7  females. 

Evidently  either  these  facts  must  be  refuted,  or  the  theory  of  the 
traumatic  causation  of  cancer  must  be  given  up. 

Still  more  cogent  is  reasoning  of  this  kind  when  applied  to  cancer  of 
the  breast ;  for,  whereas  men  are  quite  three  times  as  liable  to  traumata 
of  this  part  as  women,  yet  they  suffer  from  mammary  cancer  only  in  the 
proportion  of  16  to  1,863,  or  1  male  to  116  females. 

Moreover,  were  mammary  cancers  thus  caused,  the  nipple  and  areola 
would  be  more  frequently  affected  than  other  parts  of  the  breast ;  but, 
as  we  have  already  seen,  the  actual  proportion  of  cancers  that  arise  from 
this  part  is  less  than  1  per  cent.,  while  the  skin  of  the  mammary  region 
is  even  much  less  liable. 

This  completely  negatives  the  alleged  causation  of  mammary  cancer 
by  pressure  of  the  corset,  injury  of  the  nipple  in  suckling  etc. 

Again,  if  the  traumatic  theory  of  cancer  causation  were  true,  those 
parts  of  the  body  most  subject  to  injuries,  such  as  the  upper  and  lower 
extremities,  the  scalp  etc.,  would  be  the  commonest  seats  of  the  disease  ; 
but  its  actual  localization  is  totally  different. 

The  great  rarity  of  malignant  epithelial  tumours  of  the  extremities 
and  scalp,  has  much  significance  in  this  connexion  :  thus,  of  my  7,297 
cancer  cases,  only  99  originated  in  the  extremities  (71  in  the  lower  and 
28  in  the  upper)  ;  while  there  were  only  10  scalp  cases.  Moreover,  of  all 
parts  of  the  hand,  the  palm,  which  is  most  exposed  to  traumata,  is  least 
liable  to  cancer. 

Another  item  is,  that  the  initial  lesion  of  cancer  is  almost  invariably 
solitary  ;  whereas,  if  the  disease  were  of  traumatic  origin,  it  would  often 
be  multiple. 

It  is  a  curious  circumstance,  that  advocates  of  the  traumatic  theory 
of  cancer  causation  should  have  overlooked  these  obvious  facts. 

They  base  their  belief  in  it  on  statements  made  by  patients  them- 
selves, as  to  the  antecedent  occurrence  of  trauma.  Of  137  women 
with  mammary  cancer  interrogated  by  me,  35  gave  a  history  of  ante- 
cedent trauma,  or  25-5  per  cent.  ;  inot  her  words,  the  most  careful 
investigation  directed  expressly  to  this  point,  failed  to  elicit  any  previous 
history  of  trauma  in  74-5  per  cent,  of  all  cases. 


INFLAMMATION,  TRAUMA,  AND  OTHER  FACTORS       287 

In  not  a  single  instance  was  there  any  evidence  that  the  disease  had 
developed  out  of  induration,  or  other  obvious  lesion  thus  induced. 

In  the  cases  under  my  observation,  it  seemed  to  me  that  injury  was 
often  merely  the  means  of  directing  the  patient's  attention  to  the  pre- 
viously existing  disease,  of  which  she  had  until  then  been  unconscious. 

Of  1,000  cases  of  cancer  consecutively  under  my  observation,  there 
was  but  a  single  instance  in  which  the  disease  immediately  followed  an 
injury,  and  this  was  a  case  of  so-called  acute  traumatic  malignancy. 
Yet,  if  traumata  were  the  efficient  causes  of  cancer,  such  occurrences 
would  be  quite  common  instead  of  being  so  infinitely  rare. 

Moreover,  we  cannot  produce  cancer  by  any  kind  of  traumatism, 
even  in  those  who  are  already  subject  to  the  disease  ;  and  their  wounds 
heal  just  as  do  those  of  the  non-cancerous. 

The  attempts  made  by  Gilbert  and  Roger  1  to  produce  cancer  of  the 
mammae  of  old  bitches,  by  subjecting  them  to  various  forms  of  mechanical 
irritation,  completely  failed  to  attain  this  end  ;  and  Cazin,  by  rubbing 
soot  into  the  irritated  parts,  was  equally  unsuccessful,  although  the  soot 
was  taken  up  by  the  local  cells,  as  we  know  is  also  the  case  in  "  chimney- 
sweep's cancer." 

Though  a  blow,  wound,  or  other  injury  may  sometimes  precipitate 
the  formation  of  a  cancer  ;  yet,  it  appears  to  me  from  the  foregoing  con- 
siderations, that  such  stimuli  are  of  themselves  inadequate  to  cause  the 
disease.  I  regard  the  relation  of  trauma  to  cancer — to  borrow  a  Dar- 
winian simile — as  resembling  that  of  a  spark  in  contact  with  combustible 
matter,  the  result  depending  upon  the  nature  of  the  latter  rather  than 
upon  the  spark  itself. 

"  Traumatic  Malignancy." 

Among  the  clinical  records  of  the  last  half -century,  some  rare  instances 
may  be  found,  in  which  the  outbreak  of  malignant  disease  has  appeared 
rapidly  to  follow  severe  local  trauma  ("  acute  traumatic  malignancy  "), 
as  in  cases  reported  by  Barwell.2  H.  Cripps,  Puzey  and  others.  Careful 
study  of  the  records  of  these  rare  cases — all  of  which  are  sarcomata — 
inclines  me  to  admit  the  reality  of  this  exceptional  method  of  causation  ; 
although,  in  some  cases  of  this  kind,  the  malignant  growth  undoubtedly 
antedated  the  alleged  causative  injury,  as  was  the  condition  in  the  only 
example  that  has  come  under  my  own  immediate  notice. 

Another  group  of  cases,  nearly  akin  to  the  above,  comprises  sarcomata 
developing  at  the  seat  of  recent  fractures,  of  which  examples  have  been 
recorded  by  Shattock,3  Griffiths,4  Senn,5  Haberen,6  Pollard,?  Virchow,8 
and  others.  In  some  cases  of  this  kind — of  which  I  have  elsewhere 
reported  an  example  9 — the  tumour  preceded  and  was  the  cause  of  the 

1  La  Presse  Med.  de  Paris,  July  14,  1894. 

2  British  Medical  Journal,  1882,  vol.  i.,  p.  187,  et  seq. 

3  Transactions  of  the  Pathological  Society,  London,  1896,  vol.  xlvii.,  p.  261. 
*  British  MedicalJournal,  1884,  vol.  i..  p.  1125. 

5  "  Pathology  and  Surgical  Treatment  of  Tumours,"  1900,  p.  85. 

6  Arch.  f.  Mm.  Chir.,  Ed.  xliii.,  S.  352. 

7  Transactions  of  the  Pathological  Society,  London,  1885,  vol.  xxxvi.,  p.  388. 
"  Path,  des  Tumeurs,"  1867.  t.  i.,  p.  482. 

9  Middlesex  Hospital  Surgical  Report  for  the  Year  1888,  p.  269,  No.  4. 


288  THE  NATURAL  HISTORY  OF  CANCER 

fracture,  rather  than  vice  versa.  In  other  cases,  however,  the  disease 
probably  started  from  tumour  germs,  entangled  in  the  reparative  new 
formation,  and  incited  thereby  to  abnormal  growth  ("  callus-sarcomata  " 
etc.). 

From  the  fact  that  cartilaginous  structures  commonly  abound  in 
these  tumours,  it  may  be  inferred  that  heterotopic  elements  of  this  kind 
are  the  germs  whence  most  of  them  arise  ;  and  it  accords  with  this,  that 
some  of  these  tumours  are  of  an  osteo-chondromatous,  rather  than  of  a 
sarcomatous,  nature. 

In  like  manner,  hydatid  and  tuberculous  diseases,  sometimes  develop 
in  the  callus  of  fractures. 

Even  many  years  after  the  original  injury,  malignant  tumours  have 
been  known  to  originate  thus. 

In  other  parts  of  the  body  similar  conditions  are  very  exceptionally 
met  with  ;  e.g.,  cancer  originating  in  Rontgen-ray  burn  (C.  W.  Allen, 
Foulerton  etc.),  in  an  issue  wound  (Billroth),  in  an  empyema  wound 
(Young),  in  the  wound  after  the  operation  of  ventro-fixation  of  the  uterus 
(Malone),  in  the  scar  of  stumps  after  amputation,  in  old  scars  (especially 
of  burns),  in  chronic  sinuses  etc. 

In  like  manner,  after  the  surgical  ablation  of  non-malignant  tumours, 
in  very  rare  and  exceptional  cases,  malignant  disease  may  spring  up  in 
the  wound  :  e.g.,  after  removal  of  mammary  fibro-adenoma  (Erichsen), 
of  simple  dermoid  cyst  (Wolf),  of  "  desmoid  "  of  the  abdominal  wall 
(Asken),  of  angioma  (Pirogoff),  of  uterine  myoma  etc. 

It  is  only  after  operations  in  which  one  or  both  ovaries  have  been 
removed,  that  occurrences  of  this  kind  are  at  all  frequent ;  and  this  type 
of  case,  setiologically  regarded,  belongs  to  quite  a  different  category,  as 
I  shall  subsequently  have  occasion  to  show. 

I  have  also  seen  instances  of  the  acute  outbreak  of  malignant  disease, 
after  the  surgical  removal  of  fairly  chronic  cancers  of  the  breast,  uterus, 
cheek  etc.,  in  which  it  seemed  likely  that  the  acute  post-operative  exacer- 
bation of  the  malady,  might  be  ascribed  to  dissemination  in*fche  wound 
of  particles  of  the  disease,  detached  during  the  course  of  the  operation, 
which  had  thus  acquired  increased  capacity  for  malignant  growth. 

Perhaps  the  most  remarkable  feature  about  such  cases  as  are  com- 
prised in  this  section,  is  their  great  rarity  ;  to  account  for  this,  I  can 
only  surmise  that  the  final  outbreak  is  but  the  explosion  of  a  long  train 
of  antecedent  preparation  ;  hence  also  the  failure  of  attempts  to  repro- 
duce similar  results  experimentally  in  animals. 


CHAPTER  XII 

THE  QUESTION  OF  THE   ORIGIN  OF  MALIGNANT  FROM 
NON-MALIGNANT  TUMOURS 

IMPORTANT  practical  issues  are  involved  in  the  solution  of  this  question,, 
as  to  the  alleged  proclivity  of  non-malignant  tumours  to  become  malig- 
nant. If  any  such  tendency  really  exist,  then  non-malignant  .tumours 
ought  to  be  promptly  extirpated. 

Prior  to  the  application  of  the  microscope  to  the  study  of  new  growths, 
it  was  generally  believed  that  every  chronic  tumour  ("  scirrhous  ")  either 
was  malignant  or  tended  to  become  so.  This  dictum  was  long  ago 
stigmatized  by  Lebert 1 — who  showed  its  erroneousness — as  :  "A  very 
convenient  doctrine  for  surgeons  ";  and,  as  I  shall  proceed  to  show,  this 
criticism  still  holds  good. 

The  difficulty  of  then  discriminating  between  malignant  and  non- 
malignant  tumour-like  swellings,  rendered  some  such  belief  inevitable  ; 
but,  since  the  utilization  of  the  microscope  for  this  purpose,  it  is  sur- 
prising to  find  the  old  creed  still  so  influential. 

We  now  have  to  inquire  whether,  in  the  light  of  modern  research,  this 
belief  is  justifiable. 

Since  innocent  tumours  may  inflame,  suppurate,  ulcerate,  necrose, 
and  degenerate,  just  like  physiological  parts  of  the  body,  it  seems  not 
unreasonable  to  suppose,  on  a  priori  grounds,  that  they  may  also  become 
the  seats  of  malignant  disease.  The  occasional  coexistence  in  the  same 
organ,  of  benign  and  malignant  tumours,  favours  this  view.  Such  are 
the  chief  considerations  which  have  given  rise  to  the  common  belief,  that 
innocent  tumours  are  peculiarly  apt  to  become  malignant. 

On  critical  examination  of  the  subject,  two  considerations  have  much 
impressed  me. 

The  first  is  the  rarity  with  which  these  two  kinds  of  neoplasms  coexist 
in  the  same  organ  ;  so  that,  even  if  we  admit  that  malignant  transforma- 
tion takes  place  in  all  such  associated  neoplasms,  the  event  must  be  one 
of  great  rarity — very  much  rarer  than  it  would  be,  if  non-malignant 
tumours  were  especially  prone  to  become  malignant. 

The  second  consideration  is  the  inconclusiveness  of  the  evidence,  as 
to  the  malignant  growths  in  most  of  these  cases,  having  sprung  from  their 
non-malignant  associates.  In  many  instances,  it  is  perfectly  evident, 
that  the  association  is  a  mere  coincidence,  each  neoplasm  having  originated 
independently.  In  other  cases,  the  coexisting  neoplasms  are  more  closely 

1  "  Traitedes  Maladies  Cancereuses,"  Paris,  1851,  p.  59. 
289  19 


290  THE  NATURAL  HISTORY  OF  CANCER 

associated  ;  but,  even  in  these,  the  appearance  of  the  non-malignant 
tumours  is  often  such,  as  hardly  to  countenance  the  belief  that  the 
malignant  disease  had  sprung  from  them. 

In  short,  a  thorough  examination  of  the  subject  in  all  its  bearings  has 
convinced  me,  that  non-malignant  tumours  have  no  special  proclivity 
to  malignancy. 

In  support  of  this  thesis,  I  now  propose  to  discuss  the  evidence  in 
detail,  as  it  affects  some  of  the  more  important  organs. 


Uterine  Myoma  and  Malignant  Disease. 

It  must  be  borne  in  mind  that  uterine  myomata  are  of  very  frequent 
occurrence,  according  to  Bayle,  20  per  cent,  of  all  women  over  thirty- 
five  are  thus  affected ;  and  there  are  good  reasons  for  believing,  that  the 
liability  to  these  tumours  increases  still  more  with  advancing  years.1 

If  this  estimate  be  correct — and  so  far  as  I  can  judge  it  is  not  very 
wide  of  the  mark — these  neoplasms  are  much  commoner  even  than  cancer 
(malignant  epithelial  neoplasm).  Hence,  considering  the  great  frequency 
of  both  diseases  in  women  of  a  certain  age,  we  need  not  be  surprised  to 
find  them  coexisting  in  the  same  uterus  rather  frequently.  Thus,  of 
78  uterine-cancer  necropsies  of  my  list,  in  5  there  were  concomitant 
myomata  ;  and  of  the  45  similar  necropsies  tabulated  by  Lebert,  6  were 
associated  with  myomata  ;  thus,  in  these  123  uterine-cancer  necropsies, 
myomata  co-existed  in  11,  or  in  9  per  cent. 

In  estimating  the  significance  of  this  concomitancy,  the  following 
items  demand  special  attention. 

1.  In  the  immense  majority  of  cases — in  four-fifths  of  those  under 
my  own  observation1 — the  two  neoplasms  were  quite  separate  and  inde- 
pendent of  one  another — the  myoma  having  sprung  from  the  corpus  and 
the  cancer  from  the  cervix  or  portio — so  that,  in  these  cases,  there  could 
be  no  question  of  the  latter  disease  having  originated  from  the  former. 

2.  In  the  remaining  cases,  the  coexisting  neoplasms  were  more  closely 
associated,  most  of  them  arising  in  the  corpus.     A  common  condition  is 
to  find  one  or  more  small  subperitoneal  or  intra-mural  myomata,  with 
cancer  of  the  mucosa.     Under  these  circumstances,  the  fibroid  is  seldom 
cancerous.     Of  course,  when  the  cancerous  disease  spreads  widely,  even 
fibroids  such  as  these  may  be  at  length  invaded. 

3.  A  good  many  instances  have  been  recorded  of  myomata  projecting 
into  the  uterine  cavity,  and  bearing  on  their  surface  a  cancerous  growth 
or  ulcer.     In  cases  of  this  kind,  the  cancerous  disease  usually  spreads 
from  the  mucosa  to  the  fibroid,  by  the  way  of  the  peri  vascular  lymphatics. 
In  like  manner,  uterine  fibroids  projecting  into  the  abdomen,  sometimes 
become  cancerous  through  extension  of  the  disease  from  adherent  neigh- 
bouring organs,  such  as  the  ovary,  intestine,  and  omentum. 

4.  There  is  yet  another  way  in  which  fibroids  may  possibly  be  secon- 
darily invaded  by  cancer,  and  that  is  by  dissemination  from  a  primary 
focus  elsewhere,  of  which  Schaper  2  has  reported  an  instance,  the  primary 

1  Vide  the  author's  book  on  "  Uterine  Tumours,"  1901,  p.  123. 

2  Arch.  f.  path.  Anat.,  1892,  Bd.  cxxix.,  S.  61. 


MALIGNANT  FROM  NON-MALIGNANT  TUMOURS         291 

disease  being  in  the  lung,  and  Bender  *  a  similar  case,  secondary  to  primary 
cancer  of  the  mamma. 

5.  In  such  cases  as  the  foregoing  there  is,  of  course,  no  question  of 
the  cancerous  disease  having  primarily  originated  in  the  myoma.  Indeed, 
this  is  an  event  of  such  rarity,  that  the  great  Cruveilhier,  with  his  large 
and  carefully  recorded  experience,  never  saw  a  single  instance  of  it : 
hence  he  wrote  :2  "  Les  corps  fibreux  ne  sont  pas  susceptibles  de  degenera- 
tion cancereuse.  II  y  a  incompatibility  absolue  entre  les  corps  fibreux 
et  le  cancer."  Although  we  now  know,  that  there  is  no  such  absolute 
incompatibility  between  uterine  myoma  and  cancer,  as  Cruveilhier 
believed  ;  yet,  the  extraordinary  rarity  of  this  morbid  conjunction,  is  a 
noteworthy  and  well-determined  fact.  Thus,  notwithstanding  the  great 
activity  of  modern  pathologists,  only  about  two  dozen  instances  of  it 
have  hitherto  been  recorded ; 3  and,  in  many  of  these,  the  evidence 
adduced  as  to  the  cancer  having  originated  in  this  particular  way,  is 
far  from  being  really  convincing. 

The  frequent  presence  of  epithelial  structures  in  uterine  myomata,  as 
first  demonstrated  by  Babes  and  Diesterweg,  and  confirmed  by  Ricker, 
Orloff,  Recklinghausen,  Landau  etc.,  enables  us  to  understand  the  source 
whence  the  cancerous  disease  of  uterine  fibroids  originates. 

Cases  of  this  kind  have  been  described  by  Klob,  Coe,  Rcahrig,  Lieb- 
mann,  Legueu  and  Marien,  Roily  4  etc. 

Klob,5  in  describing  the  first  case  of  this  kind,  says  :  "  In  1862,  a  sin- 
gular specimen  was  added  to  the  Salzburg  Museum.  From  the  interior 
of  a  fibroid,  the  size  of  a  child's  head,  situated  in  the  posterior  wall  of  the 
uterus,  carcinoma  had  undoubtedly  developed,  without  any  other  portion 
of  the  uterus  being  affected  ;  and,  I  am  therefore  constrained  to  admit  the 
possibility  of  such  a  transition  ;  although  I  cannot  recall  a  second  case  of 
this  kind,  either  in  the  literature  of  the  subject,  or  in  my  rather  extensive 
experience." 

In  a  case  under  my  own  observation,  there  was  a  large,  encapsuled, 
fibroid  tumour,  the  size  and  shape  of  a  lemon,  in  the  substance  of  the 
lower  part  of  the  posterior  wall  of  the  uterus,  where  it  had  compressed  the 
rectum,  and  caused  symptoms  of  intestinal  obstruction.  This  tumour 
was  infiltrated  throughout  by  colloid  cancer  of  the  tubular  type, which 
had  also  slightly  invaded  some  of  the  adjacent  structures.  Several 
adjacent  lymph-glands  were  invaded,  but  there  were  no  metastases.  The 
patient  was  a  woman,  aged  forty-three,  who  had  complained  of  difficulty 
in  defsecation  for  the  last  twenty-five  years. 

Noble,6  having  analysed  1,188  promiscuously-gathered  myoma  cases, 
found  that  29  of  them  were  complicated  by  cancer  of  the  corpus  and  only 
12  by  cancer  of  the  cervix  ;  this  ratio  being  so  much  at  variance  with  the 
usual  standard  of  uterine-cancer  localization,  he  concluded  that  myomata 
predisposed  to  cancer  of  the  corpus.  If  his  cases  were  really  represen- 

1  Butt,  et  Mem.  Soc.  Anat.,  Paris,  October,  1904. 

2  "  Traite  d'Anat.  Path.  Gen.,"  etc.,  liv.  iii.,  p.  661. 

3  Piquand,  "  Les  Degenerescences  des  Fibro-myomes  de  1'Uterus,"  Paris,  1905.  etc. 
*  Anat.  f.  path.  Anat.,  1897,  Bd.  ol.,  S.  555. 

8  "  Path.  d.  weibl.  Geschlechtsorgane,"  1864,  S.  163. 
6  American  Medicine,  September  10,  1904. 

19—2 


292  THE  NATURAL  HISTORY  OF  CANCER 

tative,  such  a  conclusion  would  be  legitimate  ;  but  we  know  that  cancer 
of  the  cervix  is  an  easily  diagnosed  disease,  and  it  is  not  likely  that  many 
patients  thus  affected  would  be  sent  to  the  surgeon  to  be  operated  on 
for  myoma.  This  is  undoubtedly  the  explanation  of  the  paucity  of  cases 
of  cancer  of  the  cervix  comprised  in  his  list ;  hence  his  conclusion  must 
be  rejected,  as  being  essentially  misleading. 

If  such  conditions  were  of  common  occurrence,  cancer  of  the  uterus 
would  be  more  frequently  met  with  in  the  corpus  than  elsewhere,  for  it  is 
here  that  over  90  per  cent,  of  all  uterine  myomata  originate  ;  but  we  know 
that  only  about  5  per  cent,  of  uterine  cancers  arise  from  the  corpus. 

It  follows  from  what  has  been  stated  that,  far  from  uterine  fibroids 
having  any  special  proclivity  to  become  cancerous,  they  are  very  much 
less  prone  to  originate  this  disease  than  are  the  epithelial  elements  of  the 
uterus  itself. 

Some  pathologists  have  ascribed  the  association  of  cancer  with  uterine 
fibroids  to  "  irritation,"  excited  by  the  presence  of  the  latter  and  the 
consequent  hyperplasia  of  the  mucosa. 

Thorn l  has  reported  an  instance  of  this  kind,  in  which  the  cancerous 
disease  appeared  to  have  been  caused  by  the  presence  of  a  large  calcified 
fibroid.  If  this  alleged  causation  were  of  common  occurrence,  we  should 
expect  to  find  fibro-myomata  more  often  concomitant  with  uterine  cancer, 
than  with  any  other  local  variety  of  cancerous  disease. 

But  this  is  not  so,  for  myomata  coexist  with  uterine  cancer  only  in 
9  per  cent,  of  the  necropsies  ;  whereas,  I  have  found  that  they  coexist 
with  cancer  of  other  localities,  to  the  extent  of  18-5  per  cent,2  It  is 
evident,  therefore,  that  the  changes  excited  in  the  uterine  mucosa  etc., 
by  the  presence  of  myomata,  do  not  specially  predispose  to  cancer. 

Passing  now  to  the  consideration  of  the  alleged  proclivity  of  uterine 
myomata  to  become  sarcomatous,  the  first  fact  that  strikes  me  is,  the 
great  frequency  of  the  former  and  the  great  rarity  of  the  latter  disease. 
My  analysis  of  2,649  consecutive  cases  of  uterine  neoplasms  shows  883 
uterine  fibro-myomas,  and  only  2  sarcomas.  In  Gurlt's  analysis  of  4,115 
uterine  neoplasms,  the  proportion  of  fibroids  to  sarcomas  is  as  481  to  8. 

It  is  evident  from  these  data,  that  uterine  myomata  seldom  become 
sarcomatous. 

This  is  quite  in  accord  with  the  experience  of  operators,  who  have 
found  that  only  from  2  to  4  per  cent,  of  their  cases  were  complicated  by 
sarcoma.  Of  course,  even  this  proportion  of  malignant  cases,  is  far  in 
excess  of  the  average  for  myomata  in  general ;  for,  the  cases  comprised  in 
this  estimate,  were  specially  selected  as  requiring  operative  treatment. 

Among  those  who  have  recorded  series  of  cases  of  this  kind,  reference 
may  be  made  to  Evelt's 3  table  of  120  operations,  with  3  examples  of 
sarcoma ;  to  Fleischmann's  4  130  cases,  with  5  examples  of  sarcoma ;  to 
Hauber's 5  138  operations,  with  3  examples  of  sarcoma  ;  to  Ulesko- 

1  Zeite.  f.  Geb.  u.  Gyn.,  1893,  Bd.  xxviii.,  Heft  1. 

2  Of  44  breast-cancer  necropsies,  I  found  uterine  fibroid  in  5 ;  and  of  37  necropsies 
for  cancer  in  other  localities  fibroids  were  present  in  10  cases. 

3  Monats.  f.  Geb.  u.  Gyn.,  November,  1903. 
*  Wien.  med.  Woch.,  1906,  Bd.  Ivi. 

6  Zent.  f.  Gyn.,  1904,  No.  11. 


MALIGNANT  FROM  NON-MALIGNANT  TUMOURS         293 

Stroganowa's l  100  cases,  with  10  instances  of  malignant  disease  ;  to 
Runner's  2  100  cases,  with  7  examples  of  malignancy  ;  to  Cullingworth's  3 
100  cases,  with  1  example  of  malignancy ;  to  Flatau's  4  104  operations, 
with  5  instances  of  sarcoma  ;  to  Fehling's  5  series  of  409  operations,  with 
9  sarcomata  ;  to  Martin's  6  205  cases,  with  4  sarcomata  etc.  :  thus,  of  these 
1,406  operated  myomata,  39  or  3-3  per  cent,  were  sarcomatous. 

I  have  seen  it  stated,  that  cystic  myomata  are  more  prone  to  originate 
sarcoma  than  their  solid  congeners  ;  but,  I  believe  this  is  due  to  cystic 
sarcomata  and  myomata,  being  easily  mistaken  for  true  cystic  myomata. 

It  is  thus  quite  clear,  that  the  origin  of  sarcomatous  disease  from  myo- 
matous  tumours,  is  very  much  rarer  than  it  would  be,  if  these  tumours 
really  had  any  special  proclivity  that  way. 

Nevertheless,  the  fact  of  the  occasional  origin  of  sarcomatous  disease 
in  uterine  fibro-myomata,  has  been  clearly  established  by  many  well- 
recorded  examples. 

In  this  connexion,  it  must  be  remembered  that  myomata  are  of  com- 
posite build,  including  connective  tissue,  muscle  elements,  bloodvessels, 
and  lymphatics,  any  of  which  may  be  comprised  in  the  sarcomatous 
matrix.  Hence  corresponding  varieties  of  the  disease.  Thus,  when  the 
morbid  process  centres  in  the  connective  tissue,  its  elements  multiply, 
destroying  the  adjacent  fibrous  tissue,  muscle  cells  etc.  (myosarcoma,  myo- 
myxoma  etc.)  ;  when  the  bloodvessel  and  lymphatic  elements  are  chiefly 
involved,  we  get  telangiectasic  (myosarcoma  telangiectaticum),  and  lym- 
phangiectasic  varieties  (myosarcoma  lymphangiectaticum).  In  other 
instances  the  muscle  elements  are  alleged  to  be  primarily  affected,  and  to 
increase  at  the  expense  of  the  remaining  constituents  (myoma  levicellulare 
malignum).  In  their  recurrences  and  metastases,  each  of  these  varieties 
usually  breeds  true. 

The  occurrence  in  these  tumours  of  cartilaginous,  osseous,  and  other 
heterotopic  structures,  of  which  many  instances  have  now  been  reported 
(Ascher,  Feuchtwanger,  Kworostansky,  Freund,  Bidder  etc.),  seems  to 
indicate  that  this  form  of  sarcomatous  disease  may  often  be  of  pre-patal 
origin. 

Myomata  of  the  uterine  wall  may  also,  very  rarely,  be  secondarily 
invaded  by  sarcomatous  disease  of  the  overlying  mucosa,  of  which 
Whitridge  Williams  has  reported  an  instance. 

It  follows  from  what  has  been  stated,  that  the  possibility  of  benign 
uterine  tumours  taking  on  malignant  characters  cannot  be  denied  ;  but 
this  is  a  very  different  thing  from  admitting,  that  such  neoplasms  are 
specially  prone  to  become  malignant.  This  is  disproved  by  the  great 
rarity  of  the  coincidence.  Non-malignant  uterine  tumours,  have  no 
special  proclivity  to  malignant  disease  ;  on  the  contrary,  as  I  have  shown, 
they  are  much  less  prone  to  originate  such  changes,  than  are  the  morpho- 
logical elements  of  the  uterus  itself. 

Monats.  f.  Oeb.  u.  Gyn.,  September,  1902. 

Am.  Med.,  July  11,  1903. 

British  Journal  of  Obstetrics  and  Gynaecology,  January,  1902. 

Munch,  med.  Woch.,  1901,  No.  14. 

Beitr.  z.  Oeb.  u.  Gyn.,  1898,  i.,  S.  485. 

Arch.  f.  Gyn.,  1888,  Bd.  xxxii.,  S.  470. 


294  THE  NATURAL  HISTORY  OF  CANCER 

Mammary  Adenoma  and  Malignant  Disease. 

After  the  non-malignant  adenomata  ("  chronic  mammary  tumours  ") 
had  been  clearly  differentiated  from  malignant  tumours  of  the  breast  by 
Astley  Cooper,  the  partisans  of  the  old  belief  as  to  the  special  proclivity 
of  the  former  to  become  malignant,  still  persisted  in  the  old  creed.  Cooper 
himself  admitted  the  possibility  of  such  an  occurrence,  thus  he  says  : x 
"  I  believe  that  if  a  person  has  a  tumour  of  the  breast  which  is  not 
malignant,  and  that  it  remains  so  till  the  change  of  life  takes  place  ;  that 
then  an  undue  action  may  be  excited  in  the  part,  and  the  tumour  become 
scirrhous." 

In  order  to  determine  the  ratio  in  which  epithelial  cancer  arises  from 
non-malignant  mammary  tumours,  I  have  consulted  the  records  of  254 
consecutive  cases  of  mammary  cancer,  of  which  I  have  preserved 
detailed  reports  :  I  find  that,  in  this  series,  cancer  originated  in  connexion 
with  fibro-adenoma  in  only  two  instances.  In  other  words,  for  every 
case  of  cancer  that  had  originated,  under  circumstances  suggestive  of  its 
having  .sprung  from  a  fibro-adenoma,  there  were  126  cases  that  had 
evidently  originated  otherwise. 

Now  I  have  ascertained  that  the  relative  frequency  of  the  occurrence 
of  fibro-adenomatous  and  cancerous  tumours  in  the  female  breast  is  372 
to  1,863,  or  the  ratio  is  about  1  to  5. 

It  is  evident  from  these  data,  that  the  malignant  transformation  of 
fibro-adenomata  is  an  event  of  extreme  rarity — very  much  rarer  than  it 
would  be,  if  fibro-adenomata  had  any  special  proclivity  to  become 
cancerous. 

Even  when  mammary  carcinoma  is  found  in  association  with  a  non- 
malignant  tumour  of  the  part,  the  cancerous  disease  often  appears  to 
have  originated  quite  independently  of  the  latter,  as  in  cases  reported  by 
Paget,2  Bryant,3  Richet,4  Gross,6  Waldeyer  6  and  others.  I  have  met  with, 
and  elsewhere  described,7  two  somewhat  similar  cases. 

Many  instances  of  the  origin  of  sarcoma  in  association  with  mammary 
fibro-adenoma,  have  now  been  recorded.  Some  authors  even  maintain, 
that  most  sarcomata  of  the  breast  arise  in  this  way,  rather  than  from  the 
tissues  of  the  gland  itself  ;  thus,  of  eight  cases  specially  studied  by  Labbe 
and  Coyne  8  ad  hoc,  four  of  them  appeared  to  have  originated  from  old 
adenomata.  I  have  not  met  with  such  cases  in  anything  like  such  a 
large  proportion  ;  for,  among  thirty  sarcomata  of  the  breast  specially 
studied  by  me,  there  was  only  one  instance  in  which  the  malignant 
affection  arose  in  this  way.  Hence,  I  feel  bound  to  reject  Labbe  and 
Coyne's  conclusion,  which  appears  to  be  based  upon  too  narrow  an 
experience.  In  some  of  these  chronic  mammary  tumours,  we  probably 

"  Lectures  on  Surgery,"  1839,  p.  378. 
"  Lect.  Surg.  Path.,"  1853,  vol.  ii.,  p.  259. 
"  Diseases  of  the  Breast,"  1887,  p.  339. 
Le  Practicien,  1879,  No.  14,  p.  163. 
"Am.  Syst.  Gyn.,"  vol.  ii.,  p.  207. 
Arch.  f.  path.  Anat.,  Bd.  lv.,  S.  124. 
"  Diseases  of  the  Breast,"  p.  312. 
8  "  Traitedes  Tumeurs  benignes  du  Sein,"  pp.  290  and  36ct 


MALIGNANT  FROM  NON-MALIGNANT  TUMOURS         295 

have  to  do  with  sarcomatous  disease,  starting  from  overgrown  super- 
numerary mammary  sequestrations,  as  I  have  elsewhere  indicated.1 

From  what  has  been  stated,  it  may  be  concluded  that  non-malignant 
mammary  tumours,  like  their  uterine  congeners,  have  no  special  proclivity 
to  originate  malignant  disease. 


Ovarian  Cystoma  and  Malignancy. 

The  question  of  the  frequency  of  malignancy,  as  a  complication  of 
ovarian  cystomata,  has  been  much  debated  among  practitioners  ;  but, 
as  the  matter  has  seldom  been  studied  with  the  aid  of  adequate  statistical 
data,  very  little  has  been  done  to  dissipate  the  prevailing  obscurity  and 
confusion. 

In  approaching  this  tangle  with  the  object  of  getting  at  the  truth,  the 
first  item  that  strikes  me,  is  the  great  frequency  of  these  non-malignant 
ovarian  cysts  ;  and  the  great  rarity  of  any  form  of  malignant  disease  of 
ovarian  origin. 

For  instance,  of  9,701  cases  of  tumours  in  women,  under  treatment 
at  several  of  the  chief  London  general  hospitals  during  a  succession  of 
years,  I  found  that  4,036  had  non-malignant  tumours,  of  which  635  were 
ovarian  cysts,  or  6-5  per  cent,  of  the  total ;  whereas,  5,665  had  malignant 
tumours,  of  which  only  67  were  ovarian,  or  0-69  per  cent,  of  the  total. 

Gurlt's  analysis  2  of  7,776  cases  of  malignant  disease  in  women  at  the 
chief  Vienna  hospitals,  points  to  the  same  conclusion  ;  for,  in  only  78  of 
these  patients,  or  in  1  per  cent.,  did  the  disease  originate  in  the  ovary. 

If  further  evidence  as  to  the  comparative  rarity  of  malignant  disease 
of  the  ovaries  is  required,  reference  may  be  made  to  the  national  mortality 
returns  ;  thus,  the  Sixty-third  Annual  Report  of  the  Registrar-General, 
shows  that  of  15,588  women  who  died  of  malignant  disease  during  the 
year  1900,  the  ovary  was  the  part  affected  in  275  cases,  or  in  1-7  per  cent.  ; 
and  the  United  States  national  statistics  for  the  same  year,  show  a  still 
smaller  proportion  of  malignant  ovarian  disease — viz.,  less  than  1  per 
cent.  (0-9). 

The  obvious  inference  from  these  data  is,  that  non-malignant  ovarian 
cystomata  seldom  originate  malignant  disease,  and  this  conclusion 
accords  with  the  clinical  evidence,  as  furnished  by  the  record  of  long  series 
of  operated  cases  by  individual  surgeons  :  thus,  of  1,388  ovarian  tumours 
operated  on  by  the  surgeons  of  the  Johns  Hopkins  Hospital,  Swan  found 
that  only  41  were  malignant,  or  about  3  per  cent.  ;  and  Geyer,  for 
the  Wiirtzburg  clinic,  gives  the  percentage  of  malignancy  as  2-3.  , 

Here  it  seems  desirable  to  point  out  that  ovarian  cystomata  comprise 
several  different  varieties  of  tumours,  among  which  it  is  in  this  connexion, 
necessary  to  discriminate  and  set  aside  for  separate  consideration,  the 
papilliferous  and  dermoid  forms. 

It  may  be  taken  as  proved,  that  malignant  disease  may  exceptionally 
arise  from  each  of  the  different  varieties  of  cystomata  ;  but,  some  of  them 
appear  to  have  greater  proclivity  in  this  direction  than  others. 

1  "  Diseases  of  the  Breast,"  p.  73,  etc. 

2  Arch.  f.  klin.  Chir.,  1880,  Bd.  xxv.,  S.  420. 


296  THE  NATURAL  HISTORY  OF  CANCER 

The  papilliferous  ovarian  tumours — or  at  any  rate  a  considerable 
proportion  of  them — are  marked  off  from  the  other  varieties,  by  the  fact 
that  they  manifest  contagious  properties,1  that  is  to  say,  they  often 
become  diffused  throughout  the  peritoneal  sac  by  auto-implantation  of 
detached  fragments  ;  hence  their  recurrence  after  removal  in  situ,  or  in 
some  part  of  the  operation  wound,  is  frequent.  Moreover,  the  disease  is 
generally  bilateral — in  over  68  per  cent,  of  the  total  cases,  according  to 
Pfannenstiel.  It  is  necessary  to  distinguish  this  form  of  local  diffusion, 
from  the  very  different  generalization  of  malignant  disease,  with  which 
it  is  undoubtedly  often  confounded.  It  is  probably  owing  chiefly  to  this 
cause,  that  papilliferous  ovarian  tumours  have  acquired  a  special  reputa- 
tion for  malignancy ; 2  and  the  fact  that  primarily-arising  ovarian  cancer, 
sometimes  assumes  the  papillary  form  ab  initio,  has  tended  to  the  same 
end. 

When  due  allowance  has  been  made  for  these  sources  of  error,  it  is 
doubtful  whether  there  is  any  justification  for  the  general  belief,  in  the 
special  proclivity  to  malignancy,  of  these  papilliferous  tumours.  The 
researches  of  Pfannenstiel,3  Semb  4  and  others,  specially  point  to  this 
conclusion  ;  with  which  the  fact  that  papillomata  in  general,  manifest  no 
such  proclivity,  also  accords. 

The  rather  numerous  cases  reported  in  comparatively  recent  times,  of 
the  supervention  of  malignant  disease — in  both  its  epithelial  and  con- 
nective tissue  forms — in  connexion  with  dermoid  and  teratoid  ovarian 
tumours,  suggest  that  these  formations  may  have  special  proclivity  that 
way ;  but,  in  the  absence  of  the  requisite  numerical  data,  nothing  more 
definite  can  be  said. 

With  regard  to  the  other  and  commoner  varieties  of  ovarian  cysts, 
which  after  all  comprise  the  great  majority,  there  is  a  consensus  of  opinion, 
that  they  have  no  special  proclivity  to  malignancy  ;  and  this  accords  with 
the  data  revealed  by  my  statistical  research,  as  previously  mentioned. 
When  therefore  it  is  stated  that,  from  a  practical  standpoint,  "all 
ovarian  tumours  must  be  regarded  as  malignant  until  removed  and 
proved  otherwise,"  I  reply  that,  although  this  may  be  "a  very  con- 
venient doctrine  for  surgeons,"  it  is  certainly  not  in  conformity  with  the 
facts  revealed  by  a  scientific  examination  of  the  subject. 

In  other  parts  of  the  body,  where  I  have  specially  studied  the  question, 
I  have  found  that  this  conclusion  is  equally  valid. 

In  like  manner  Semon5  reports,  that  of  10,747  non-malignant,  intra- 

1  The  ensemble  of  the  characters  of   these  growths  indicate  their  affinity  with  the 
genital  condylomata ;  and,  like  the  latter,  they  are  probably  transmitted  during  sexual 
intercourse,  either  with  or  without  some  other  venereal  malady,  such  as  gonorrhoea, 
syphilis,  etc.     To  this  it  may  be  objected  that,  although  growths  of  this  kind  are  recog- 
nized as  occurring  in  the  vagina,  portio,  and  tube,  they  have  never  been  met  with  in  the 
uterus.     The  answer  is  that  these  lesions  also  occur  in  the  uterus,  where  they  are  com- 
monly confounded  with  certain  hypertrophic  forms  of  chronic  endometritis,  adenoma, 
and  even,  in  rare  cases,  with  villous  cancer,  etc.     In  this  connexion  we  must  remember 
that  it  is  only  in  comparatively  recent  times— thanks  to  the  publications  of  Doran, 
Doleris,  etc. — that  the  occurrence  of  similar  papillomatous  growths  in  the  Fallopian 
tubes  has  been  discriminated ;  and  even  now  the  identity  of  the  latter  with  condylomata 
is  not  recognized  by  gynaecologists. 

2  Gebhard,  "  Path.  Anat.  d.  weibl.  Sexualorgane,"  1899,  S.  356. 

3  Veit's  "  Handb.  d.  Gynakologie,"  1898,  Bd.  iii. 

*  Norsk.  Mag.  f.  Laegeridensk,  October,  1896.  5  Cent.  f.  Chir.,  1890,  S.  463. 


MALIGNANT  FROM  NON-MALIGNANT  TUMOURS         297 

laryngeal  neoplasms,  whose  history  had  been  studied  by  him,  there 
were  only  47  instances  in  which  malignant  disease  had  supervened. 

It  follows  from  what  has  been  stated,  that  the  possibility  of  benign 
tumours  subsequently  developing  malignant  characters,  has  been 
thoroughly  proved  ;  but  this  is  a  very  different  thing  from  admitting 
that  such  tumours  are  specially  prone  to  malignancy.  This  is  disproved 
by  the  extreme  rarity  of  the  coincidence.  Non-malignant  tumours  are, 
in  fact,  less  liable  to  originate  malignant  disease,  than  are  the  normal 
morphological  elements  of  the  body  itself. 


CHAPTER  XIII 

MULTIPLE  PRIMARY  CANCER  ;  AND  THE  ASSOCIATION  OF 
CANCER  WITH  OTHER  TUMOURS 

A  PECULIAR  feature  of  cancer  is,  that  the  initial  lesion  is  generally  solitary. 
The  researches  of  Hauser  and  Petersen  into  the  architecture  of  small 
cancerous  nodules,  by  serial  sections  and  reconstruction  models,  show 
that  the  disease  spreads  in  a  multicentric  manner,  each  ingrowing  column 
being  an  outgrowth  from  the  original  germ,  and  therefore  at  first  con- 
tinuous with  it.  It  is  now,  however,  generally  recognized,  that  excep- 
tionally the  disease  springs  up  from  more  than  a  single  original  germ  ; 
and  it  is  this  that  constitutes  primary  multiplicity,  as  the  term  is  here 
employed. 

Pathologists  have  been  aware  of  this  for  some  time,  although  it  is 
only  recently  that  the  subject  has  attracted  special  attention.  Such 
cases,  however,  are  decidedly  rare.1  The  wonder  is  that  they  do  not 
occur  more  frequently,  especially  if — as  alleged — cancer  is  a  parasitic 
disease.  By  some,  however,  this  peculiarity  has  been  taken  to  indicate 
analogy  with  certain  specific  diseases,  the  virus  of  which — when  intro- 
duced into  the  system — confers  immunity  for  a  longer  or  shorter  period. 
The  ensemble  of  the  indications,  as  previously  mentioned,  is,  however, 
decidedly  against  the  acceptance  of  this  suggestion. 

Such  indications  seem  to  me  rather  to  imply,  that  the  solitariness  of 
the  initial  lesion  of  cancer  is,  in  its  origin,  akin  to  the  solitariness  of  most 
non-malignant  tumours,  and  developmental  anomalies  per  excessum. 

At  any  rate,  it  is  worth  noting  in  this  connexion,  that  all  non-malignant 
tumours  are  occasionally  multiple  in  origin  ;  and  some  of  them,  such  as 
uterine  myomata,  frequently  manifest  initial  multiplicity. 


Bilateral  Manifestations. 

Among  the  numerous  cases  of  the  multiple  outbreak  of  malignant 
disease  lately  reported,  some  of  the  most  striking  are  those  in  which  the 
malady  arises  concurrently  in  both  of  paired  organs,  or  in  both  of  other 
bilaterally  symmetrical  parts  of  the  body.  These  bilateral  tumours  are 
often  described  as  symmetrical  :  but,  it  is  very  seldom  that  the  con- 
comitant tumours  correspond  so  exactly,  as  to  justify  the  use  of  this  term. 

1  Of  1,664  cases  of  mammary  cancer  tabulated  by  Gross,  only  2  were  bilateral  in 
origin ;  but  Billroth  met  with  3  instances  of  this  kind  in  245  mammary  cases ; 
according  to  Nicholls,  of  685  necropsies  for  cancer  in  Montreal  hospitals,  18  showed  initial 
multiplicity. 


MULTIPLE  PRIMARY  CANCER  299 

A  considerable  proportion  of  bilateral  malignant  tumours  are  met  with 
in  early  life,  and  are  of  congenital  origin,  many  of  these  obviously  arising 
in  connexion  with  gross  developmental  lesions.  In  other  cases  of  this 
kind,  there  is  often  evidence  of  the  malignant  disease  having  supervened 
on  some  antecedent  morbid  condition,  such  as  eczema,  seborrhoea  etc. 

Non-malignant  tumours  of  bilateral  origin,  are  even  less  exceptional 
than  their  malignant  congeners. 

Of  course  care  must  be  taken  to  discriminate  these  primarily  arising 
bilateral  malignant  tumours,  from  secondary  forms,  due  to  bilateral  dis- 
semination from  a  remote  primary  source,  e.g.,  stomach,  thyroid,  prostate 
etc.,  as  also  from  local  disseminative  lesions,  whether  continuous  or  dis- 
continuous ;  and  this  is  sometimes  by  no  means  easy. 

Subjoined  I  submit  a  few  remarks,  as  to  the  leading  features  of  some 
of  the  chief  local  varieties  of  these  bilateral  outbreaks. 

Mamma. — I  have  elsewhere  described 1  an  example  of  bilateral  cancer 
of  the  female  breast ;  and  referred  to  similar  cases  by  Aitken,  Volkmann, 
Klotz,  Terrillon  and  others.  In  all  of  these  instances,  the  malady  was 
concomitant  with  the  puerperal  state,  its  onset  was  acute,  and  its  pro- 
gress very  rapid  ;  hence  Klotz  has  described  the  condition  as  "  Mastitis 
carcinomatosa  gravidarum  et  lactantium."  Billroth2  has  described  an 
instance  of  acute  bilateral  sarcomatous  disease  of  the  breast,  in  a  preg- 
nant woman.  This  type  of  malignant  disease  seems  to  be  relatively  less 
rare  than^the  epithelial  form  ;  for,  of  Gross's  156  cases  of  mammary  sar- 
coma, 3  were  bilateral. 

Mammary  fi.bro-adenom.ata  may  also  be  bilateral,  for  of  46  cases 
studied  by  me,  in  1  instance  there  were  several  small  tumours  in  both 
breasts  ;  and  of  Velpeau's  54  cases,  5  were  bilateral. 

It  is  by  no  means  rare  to  see  cancer  of  one  breast  followed,  after  a 
time,  by  outbreak  of  the  disease  in  the  other.  The  great  majority  of 
these  cases  are,  however,  due  to  direct  extension  of  the  primary  disease, 
or  to  its  dissemination.  Yet  it  occasionally  springs  up  independently 
in  the  opposite  breast ;  and  I  have  elsewhere  3  reported  a  case  of  this  kind. 

I  have  also  there  cited  several  remarkable  instances  in  which,  many 
years  after  extirpation  of  one  breast  for  cancer  without  recurrence,  the 
disease  subsequently  supervened  in  the  opposite  breast. 

Other  instances  of  bilateral  malignant  disease  of  the  breast,  in  which 
the  concomitant  tumours  were  of  different  anatomical  structure,  may 
also  be  mentioned  in  this  category. 

Thus,  Lebert 4  long  ago  described  an  example  of  colloid  cancer  of  one 
breast,  concomitant  with  ordinary  scirrhus  of  the  other. 

In  like  manner,  Nunn  5  has  met  with  tubular  cancer  of  the  left  breast, 
coexisting  with  atrophic  acinous  cancer  of  the  right  breast :  Mandry 6 
and  Kiister  7  have  had  similar  finds. 

Instances  of  scirrhous  cancer  of  one  breast,  concomitant  with  sarcoma 

My  book  on  "  Diseases  of  the  Breast,"  1894,  p.  318. 

Deutsche  Chir.,  Lief,  xli.,  S.  27.  3  "  Diseases  of  the  Breast,"  1894,  p.  302. 

Arch.  f.  path.  Anat.,  Bd.  iv.,  S.  216. 

Transactions  of  the  Pathological  Society,  London,  1890,  vol.  xli.,  p.  224. 
Beitr.  z.  klin.  Chir.,  1892,  Bd.  viii.,  S.  589. 

Cited  in  Michelsohn's  Inaug.  Diss.  "  Zur  Multiplicity  der  primaren  Carcinomen," 
Berlin,  1889. 


300  THE  NATURAL  HISTORY  OF  CANCER 

of  the  other,  have  been  described  by  De  Morgan,  Czerny,  Bryant,  and 
Billroth.i 

Ovary. — Malignant  tumours  of  the  ovaries  are  often  bilateral  in  origin. 
This  is  especially  the  case  with  sarcomatous  kinds,  a  large  proportion  of 
which  occur  in  early  life  :  thus  of  23  ovarian  sarcomata  studied  by  Pick, 
9  were  bilateral — of  which  latter,  6  were  of  the  small  round-celled  variety. 
Examples  of  bilateral  glandular  ovarian  cancer  have  been  studied  by 
Woolley,2  Nicholls,3  and  others  ;  while,  in  a  patient  aged  seventy,  Fran- 
genheim  4  met  with  glandular  cancer  of  both  ovaries,  together  with  endo- 
thelioma  of  the  dura  mater.  Here  also  mention  may  be  made  of 
Ladinski's5  remarkable  case  of  glandular  cancer  of  one  ovary,  with 
sarcoma  of  the  other,  in  a  patient  with  absence  of  the  uterus,  vagina, 
and  tubes. 

Examples  of  the  development  of  cancer  in  the  sound  ovary,  after 
the  removal  of  its  cancerous  fellow,  have  been  reported  by  Le  Gemtel 6 
and  others. 

With  regard  to  the  initial  multiplicity  of  non-malignant  ovarian 
tumours,  I  need  only  mention  that  it  is  of  frequent  occurrence,  especially 
in  the  dermoid,  papillary  and  cystic  forms. 

Here  it  seems  desirable  to  mention,  that  bilateral  malignant  ovarian 
tumours  are  fairly  often  met  with,  as  the  result  of  dissemination  from 
primary  growths  situated  in  the  stomach,  intestines,  other  abdominal 
viscera  etc.  ;  and  it  is  probable  that  some  of  the  bilateral  ovarian  growths, 
called  "  Krukenberg's  tumour,"  are  really  of  this  nature. 

In  this  connexion  it  should  also  be  borne  in  mind,  that  secondary 
malignant  ovarian  disease  is  relatively  much  more  frequent  than  the 
primary  form,  especially  in  adults.  On  the  other  hand,  post-mortem 
records  show,  that  gastro-intestinal  cancers  seldom  disseminate  in  the 
ovaries. 

Testis. — It  is  by  no  means  very  rare,  for  malignant  tumours  of  the 
testis  to  be  bilateral  in  origin  ;  and  this  seems  to  be  of  more  frequent 
occurrence  with  the -round- celled  sarcomata,  than  with  other  forms  of 
the  disease. 

A  considerable  proportion  of  these  malignant  testicular  tumours,  arise 
in  infancy  and  early  life  ;  and  many  of  them  are  congenital. 

In  a  remarkable  congenital  case  reported  by  Rogers,  both  testes, 
which  had  not  descended,  were  sarcomatous,  causing  a  large  intra- 
abdominal  tumour,  which  proved  a  serious  obstacle  to  delivery. 

Malignant  testicular  tumours,  especially  those  of  early  life,  are 
remarkable  for  the  great  frequency  with  which  heterotopic  structures — 
such  as  cartilage,  bone,  striped  muscle  etc. — occur  in  them. 

Of  15  early- life  testicular  malignant  tumours  tabulated  by  Schubert, 
3  were  bilateral ;  and  of  93  cases — mostly  adults — analysed  by  Kober, 
5  were  bilateral. 

For  abstracts,  vide  my  book  on  "  Diseases  of  the  Breast,"  p.  307. 

Boston  Medical  and  Surgical  Journal,  1903,  No.  1,  p.  1. 

Montreal  Medical  Journal,  1903,  p.  326. 

Arch.  f.  path.  Anat.,  1906,  Bd.  clxxxiv.,  S.  201. 

American  Journal  of  Obstetrics,  July,  1898. 

Butt,  et  Mem.  Soc.  Anat.  de  Paris,  1906,  No.  6,  p.  470. 


MULTIPLE  PRIMARY  CANCER  301 

Kidney. — Malignant  tumours  of  the  kidney  are  decidedly  rare,  except 
in  infancy  and  early  life,  when  many  cases  are  met  with,  a  considerable 
proportion  of  which  are  congenital,  and  bilateral  in  origin.  As  pre- 
viously mentioned,1  it  was  by  studying  a  case  of  a  bilateral  renal  sarcoma 
in  a  young  infant,  that  the  "  rest  "  theory  of  tumour  formation  was 
suggested  to  Cohnheim.  According  to  Paul,2  about  half  of  these  early- 
life  renal  sarcomata  are  bilateral ;  but  Walker,3  from  an  analysis  of  141 
recorded  cases,  finds  that  this  proportion  of  bilateral  cases  is  much  too 
high,  only  10  of  his  cases  being  bilateral. 

Bilateral  origin  is,  however,  of  much  more  frequent  occurrence  in 
early-life  sarcomata,  than  in  any  of  the  malignant  renal  tumours  of  more 
advanced  life,  although  bilateral  forms  of  the  disease  are  occasionally 
met  with  even  then  ;  thus,  in  an  epileptic,  male  idiot,  aged  forty-four, 
Scheren  4  found  a  sarcomatous  "  mixed  "  tumour  of  each  kidney,  together 
with  cylinder-celled  cancer  of  the  stomach,  and  multiple  psammo- 
sarcoma  of  the  brain. 

Adrenal. — In  infants  and  adults  bilateral  forms  of  malignant  adrenal 
tumours  are  occasionally  seen  :  Rolleston  and  Marks,  in  26  tabulated 
cases  at  all  ages,  met  with  2  instances  of  this  kind. 

A  case,  which  conclusively  proves  the  bilateral  origin  of  the  disease, 
had  been  recorded  by  Breton  and  Looten.5 

The  patient,  a  woman  aged  fifty-seven,  having  suffered  for  some  time 
from  symptoms  of  adrenal  insufficiency,  with  a  painful  intra-abdominal 
tumour,  died  suddenly.  At  the  necropsy,  each  adrenal  was  enormously 
,  enlarged  by  small  round-celled  sarcomatous  growth,  which  had  secon- 
darily invaded  and  caused  enlargement  of,  each  corresponding  kidney, 
and  the  adjacent  mesenteric  glands.  No  other  organs  were  involved. 
Similar  cases  have  been  reported  by  Frankel,6  Woolley,7  Suchardt  and 
others.  Adenoma  of  both  adrenals  has  also  been  met  with.8 

Eye. — Choroidal  sarcomata  are  occasionally  bilateral :  this  was  so  in 
5  of  214  cases  studied  by  Fuchs. 

With  glioma  of  the  retina  bilaterality  is  of  more  frequent  occurrence, 
and  many  congenital  cases  of  this  kind  have  been  reported — indeed,  con- 
genital glioma  is  usually  bilateral.  Of  60  cases  of  glioma  retinse  analysed 
by  Lawford  and  Collins,  in  12  the  disease  appeared  to  be  bilateral  in 
origin  ;  of  Hirschberg's  60  cases,  14  were  bilateral ;  and  of  Wintersteiner's 
405  cases,  97  were  bilateral. 

Brault  has  met  with  bilateral  congenital  ocular  lipoma. 

Ear. — Instances  of  the  bilateral  outbreak  of  epithelioma  of  the  external 
ear,  have  been  described  by  Mandry9  and  Sumpter.10  In  the  latter's 
patient,  "  cancer  "  of  the  lip  had  been  extirpated  nine  years  previously, 
without  recurrence.  In  all  these  cases  the  malignant  disease  supervened 
on  chronic  eczema  of  the  part. 

1  Chapter  VII.  2  Liverpool  Med.-Chir.  Journal,  January,  1898. 

3  Annals  of  Surgery,  1898,  vol.  xxvi.,  p.  529. 

*  Cited  by  Walter  ( Arch.  f.  klin.  Chir.,  1896,  Bd.  53). 

5  Le  Nord.  Med.,  August  15,  1905.  6  Arch.  f.  path.  Anat.,  Bd.  ciii.,  S.  244. 

7  Boston  Medical  and  Surgical  Journal,  1903,  No.  1. 

8  Warthin,  Arch,  of  Pediatrics,  1901,  p.  812. 

9  Beitr.  z.  klin.  Chir.,  1892,  Bd.  viii.,  S.  589. 

10  Lancet,  1893,  vol.  i.,  p.  887  ;  also  ibid.,  1894,  vol.  i.,  pp.  1160  and  1274. 


302  THE  NATURAL  HISTORY  OP  CANCER 

Extremities. — Of  263  cases  of  primary  cancer  of  the  extremities 
analysed  by  Michael,1  two  were  bilateral  and  approximately  symmetrical  : 
in  one  of  these  cases  the  cancerous  disease  supervened  on  chronic  varicose 
ulcers. 

Massen  has  reported  bilateral  congenital  myxosarcoma  of  the  gluteal 
region. 

It  is  evident  from  these  notes,  that  the  bilateral  outbreak  of  malignant 
disease  in  paired  organs,  is  less  exceptional  than  is  generally  believed,  even 
when  liberal  allowance  has  been  made  for  possible  sources  of  error. 

Other  Examples  of  Primary  Multiplicity. 

Skin. — In  no  part  of  the  body  does  the  initial  outbreak  of  cancer,  so 
frequently  manifest  itself  in  the  form  of  multiple  foci,  as  in  the  skin — 
especially  the  skin  of  the  face.  In  these  cases,  hyperplastic  changes  of 
the  integument  or  other  lesions,  almost  invariably  coexist ;  and  workers 
in  certain  irritating  substances  such  as  tar,  paraffin,  soot  etc.,  are  rela- 
tively often  affected. 

I  have  elsewhere  2  described  the  case  of  an  asphalter,  aged  seventy-two, 
with  three  widely-separated,  independent  cancerous  lesions  on  different 
parts  of  the  face,  associated  with  "  chronic  seborrhcea." 

Two  of  these  lesions  were  ordinary  epidermoidal  cancer,  while  the 
third  was  cylinder-celled,  sweat-gland  cancer. 

Similar  cases  have  been  reported  by  Volkmann,3  Tillmanns,4  Schim- 
melbusch,6  and  others.  In  chimney-sweeps  I  have  seen  the  scrotal 
integument  similarly  affected.  Tillmans  has  met  with  an  instance  of 
epithelioma  of  the  integument  of  the  forearm  and  of  the  scrotum,  in  a 
paraffin  worker.  In  old  persons,  multiple  cutaneous  cancers  sometimes 
arise  in  connexion  with  chronic  seborrhcea.  Primary  multiplicity  is  also 
often  met  with  in  cases  of  rodent  ulcer,6  especially  in  aged  subjects  ;  and 
Bowlby  7  has  seen  six  distinct  lesions  of  this  kind  in  one  patient. 

Examples  of  multiple  cancer  of  the  skin  of  the  face,  supervening  on 
lupous  ulceration,  have  been  recorded  by  Steinhauser,  Bayha  and  others. 
It  will  be  noticed  that  in  most  of  the  cases  just  mentioned,  the  outbreak 
of  the  cancerous  disease  appears  to  have  been  precipitated  by  some  form 
of  antecedent  lesion  ;  which,  it  may  be  surmised,  acted  as  fuel  to  the  fire 
of  pre-existing  epithelial  proliferation. 

Schimmelbusch  has  described  epidermoidal  cancer  of  the  skin  of  the 
nape  of  the  neck,  concomitant  with  the  same  kind  of  cancer  of  the  skin 
of  the  ear  ;  also  the  same  kind  of  cancer  of  the  ear  and  lower  Hp. 

Tillmanns,  in  like  manner,  found  the  skin  of  the  scrotum  and  forearm 
concurrently  affected  ;  and  C.  Thompson  8  the  skin  of  the  scrotum,  thigh 
and  calf  of  one  leg.  Beatson 9  met  with  rodent  ulcer  of  the  face,  in 

Beitr.  z.  Jdin.  Chir.,  Bd.  vii.,  S.  13. 

Twentieth  Century  Practice  of  Medicine,  1898,  vol.  xvii.,  p.  228. 

Sam.  klin.  Vortrage,  No.  257.  *  Deutsche  Zeits.  f.  Chir.,  1880. 

Arch.  f.  klin.  Chir.,  1880. 

For  cases,  vide  Hutchinson's  "  Archives  of  Surgery,"  1891,  vol.  iii.,  pp.  318  and  335. 

Transactions  of  the  Pathological  Society,  London",  1894,  vol.  xlv.,  p.  163. 

8  Practitioner,  October,  1899,  p.  414. 

9  British  Medical  Journal,  1899,  vol.  ii.,  p.  1602. 


MULTIPLE  PRIMARY  CANCER  303 

association  with  epidermoidal  cancer  of  the  skin  of  one  hand,  and 
cutaneous  papilloma  of  the  other  hand  ;  Winiwarter,1  three  years  after 
excision  of  epidermoidal  cancer  of  the  lower  lip,  without  recurrence,  found 
cutaneous  cancer  of  the  root  of  the  nose  ;  and  Becker  2  met  with  rodent 
ulcer  of  the  left  ala  nasi,  and  similar  disease  of  the  right  ear,  together 
with  melano-sarcoma  of  the  right  cheek,  the  patient  being  also  affected 
with  congenital  angiomaof  the  left  cheek,  pigmen ted  hairy  mole  of  the  fore- 
head, as  well  as  with  comedones,  chronic  seborrhoea,  acne  of  the  face  etc. 

Many  examples  of  primary  multiple  sarcoma  of  the  skin  have  also 
been  recorded  in  children  and  adults,  several  of  the  former  being  con- 
genital (Karewski  etc.)  ;  but,  the  whole  subject  of  sarcoma  of  the  skin, 
and  its  relation  to  other  morbid  conditions,  is  in  such  a  confused  and 
unsatisfactory  condition,  that  I  must  be  excused  from  entering  further 
into  the  matter  here. 

As  examples  of  the  outbreak  of  the  disease  concurrently  in  the 
integument  and  other  parts  of  the  body,  the  following  cases  may  be 
mentioned  : — epidermoidal  cancer  of  the  skin  of  the  foot,  with  columnar- 
celled  cancer  of  the  gastric  mucosa  by  Cordes ; 3  epidermoidal  cancer  of 
the  skin  of  the  abdomen,  and  cancer  of  the  pyloric  mucosa  by  Hutchin- 
son  ;  4  I  have  seen  rodent  ulcer  of  the  face,  in  a  man  from  whose  lower  lip 
epidermoidal  cancer  had  been  excised  fifteen  years  previously,  without  re- 
turn of  the  original  disease  ;  cancer  of  the  stomach,  in  a  man  whose  ear  had 
previously  been  extirpated  for  epidermoidal  cancer,  by  Billroth ; 5  epider- 
moidal cancer  of  the  skin  of  the  face,  with  spheroidal-celled  cancer  of  the 
pyloric  mucosa,  by  Klebs  ;  6  epidermoidal  cancer  of  the  skin  of  the  upper 
eyelid,  with  cylinder-celled  cancer  of  the  rectal  mucosa,  by  Kaufmann ; 7 
rodent  ulcer  of  the  face  of  fourteen  years'  duration,  with  sarcoma  of  the 
antrum  of  the  superior  maxilla  by  Langton  8  etc. 

Uterus. — In  the  uterus,  as  in  most  other  parts  of  the  body,  the 
initial  manifestation  of  cancer  is  nearly  always  solitary ;  but  a  few 
instances  of  primary  multiplicity  have  lately  been  recorded. 

Thus  Hofmeier,  Winter,  Schauta  and  Binswanger  have  reported  cases, 
in  which  epidermoidal  cancer  of  the  portio,  was  concomitant  with 
cylinder-celled  glandular  cancer  of  the  corpus  or  cervix  ;  John  Williams 
met  with  an  instance,  in  which  two  separate  columnar-celled  glandular 
cancers  of  the  canalis  cervicalis,  were  associated  with  epidermoidal  cancer 
of  the  portio  ;  while  Hitschmann,  Kaufmann,  Lewers  and  others  have 
found  epidermoidal  cancer  of  the  corpus  (including  ingrowths  and 
"nests"),  combined  with  cylinder-celled  adeno-carcinomaof  the  same  part. 

The  infantile  type  of  uterine  sarcoma  is  generally  congenital,  and 
multiple  ab  initio  ;  and,  even  among  adult  forms  of  uterine  sarcoma, 
primary  multiplicity  is  occasionally  seen,  especially  in  those  of  mucosal 
origin. 

Examples  of  concomitant  uterine  epithelioma  and  sarcoma,   have 

"  Beitr.  z.  Stat.  d.  Carcinom.,"  1878.  2  Beitr.  z.  klin.  Chir.,  Bd.  xiv.,  S.  146. 

Arch.  f.  path.  Anat.,  1896,  Bd.  cxlv.,  S.  422. 

"  Archives  of  Surgery,"  vol.  iii.,  p.  47. 

Cited  by  Mercanton  (Rev.  Mid.  de  la  Suisse  rom.,  1893,  No.  3,  p.  173). 

Arch.  f.  path.  Anat.,  Bd.  cxl.  7  Ibid.,  1879. 

St.  Bartholomew's  Hospital  Reports,  1888,  vol.  xxiv.,  p.  284. 


304  THE  NATURAL  HISTORY  OF  CANCER 

been   recorded   by   Montgomery,    Niebergall,    Keller,    Emanuel,    Rabl- 
Riickhardt,  Franque  and  others. 

In  Montgomery's 1  case,  cancer  of  the  cervix  was  associated  with 
sarcoma  of  the  corpus  ;  while  in  Niebergall's,2  both  forms  of  malignant 
disease  were  present  in  the  corpus,  together  with  myoma  and  mucosal 
polypi.  Milford3  had  previously  described  an  instance  of  concomitant 
melanotic,  myxomatous,  myomatous  and  cystic  uterine  tumours. 

I  have  elsewhere4  given  examples  of  multiple  malignant  uterine 
growths,  due  to  the  spread  of  the  disease  by  auto-implantation  and 
dissemination. 

Cases  illustrating  the  independent  outbreak  of  cancer  in  the  breast  and 
uterus,  have  been  carefully  studied  by  Richter,5  Beadles,6  Young,7  Mer- 
canton  8  (three  cases),  Broca  9  etc. 

Richter's  and  Beadle's  patients  were  concurrently  affected  with 
epidermoidal  cancer  of  the  cervix  uteri,  and  acinous  glandular  cancer  of 
the  mamma.  In  a  case  of  this  kind  by  Walter,10  ovarian  cystoma  was 
also  present. 

Russell  (of  Baltimore  xl)  has  described  cases  in  which — after  vaginal 
hysterectomy  for  cancer  without  local  recurrence — cancer  of  the  breast 
subsequently  developed  independently. 

The  independent  outbreak  of  cancer  in  the  breast,  uterus,  and  ovary 
has  been  signalized  by  Walter ; 12  in  the  vulva,  breast  and  uterus  by 
Zeiss  ;13  in  the  uterus  and  vagina  by  Mercanton;14  in  the  uterus  and  vulva 
by  Mercanton  ;  in  the  uterus  and  Fallopian  tube  by  Hafbauer  ; 16  in  the 
uterus  and  ovaries  by  Reichel 16  and  others  ;  in  the  uterus  (epidermoidal 
cancer  of  the  cervix)  and  pancreas  (cylinder-celled  glandular  cancer)  by 
Bard ; 17  the  same  variety  of  uterine  cancer,  concomitant  with  cylinder- 
celled  cancer  of  the  sigmoid  colon  by  Beck  ; 18  in  the  uterus  (epidermoidal 
cancer)  and  thyroid  (adeno-carcinoma)  by  Richter ; 19  in  the  uterus  and 
stomach  by  Walshe,20  Kronig  21  etc. 

An  elderly  lady,  one  of  whose  eyes  had  been  extirpated  by  Hutchin- 
son22  for  melanotic  sarcoma,  died — free  from  any  return  of  the  original 
disease — ten  years  afterwards,  of  cancer  of  the  uterus. 

Hanot 23  found  cancer  of  the  liver,  coexisting  with  sarcoma  of  the 
uterus  ;  Schmincke,24  cylinder-celled  cancer  of  the  gall-bladder,  likewise 
with  sarcoma  of  the  uterus  ;  and  Luminezen  sarcoma  of  the  vagina,  with 
epithelial  cancer  of  the  uterus.25 

Mamma. — An  example  of  epidermoidal  cancer  of  the  nipple,  with 

1  Occidental  Medical  Times,  1893,  p.  311.  2  Arch.  f.  Gyn.,  Bd.  1.,  Heft  1,  S.  129. 

3  New  Smith  Wales  Medical  Gazette,  1873-1874,  vol.  iv.,  p.  163.  4  Chapter  VIII. 

6   Wien.  klin.  Woch.,  August  17,  1905,  S.  865. 

6  Transactions  of  the  Pathological  Society,  London,  1897,  vol.  xlviii.,  p.  236. 

7  Archives  of  the  Middlesex  Hospital,  1904,  vol.  iii.,  p.  165. 

8  fiev.  Med.  de  la  Suisse  Somande,  1893,  No.  3,  p.  173. 

9  "  Traite  des  Tumeurs,"  1866,  t.  i.,  p.  284.         10  Arch.  /.  Jclin.  Chir.,  1896,  Bd.  liii. 
11  Johns  Hopkins  Hospital  Bulletin,  December',  1899.  12  Op.  cit. 

*3  Cent.  f.  Gyn.,  1892,  No.  40.  1J  Op.  cit. 

15  Arch.  f.  Gyn.,  Bd.  Iv.,  S.  316.  16  Zeits.  f.  Geb.  u.  Gyn.,  1880,  Bd.  xv. 

17  Arch.  gin.  de  Med.,  1892,  p.  541.  18  Prag.  med.  Woch.,  1883. 

19  Op.  cit.  20  "  Nature  and  Treatment  of  Cancer,"  1846. 

21  Cent.  f.  Gyn.,  1902,  No.  30.  22  Archives  of  Surgery,  vol.  iii.,  No.  9,  p.  48. 

23  Cited  by  Bard.  24  Arch.  f.  path.  Anat.,  1906,  Bd.  clxxxiii.,  S.  160. 

25  Pest.  med.  chir.  Presse,  1878,  xiv.,  p.  176. 


MULTIPLE  PRIMARY  CANCER  305 

concomitant  acinous  glandular  cancer  of  the  same  breast,  has  been 
recorded  by  Morestin ; l  and  some  cases  of  so-called  "  Paget's  disease," 
undoubtedly  belong  to  the  same  category. 

In  a  single  breast,  mixed  malignant  tumours — comprising  sarcomatous 
and  epitheliomatous  elements — have  also  been  reported  (Heurtaux,  Coen 
etc.),  to  which  reference  has  been  made  in  a  previous  chapter.2 

I  have  elsewhere  3  recorded  the  case  of  an  elderly  woman  who,  having 
suffered  for  seven  years  from  "  rodent  ulcer  "  of  the  face,  then  developed 
cancer  of  the  mammary  gland.     She  was  also  subject  to  uterine  myo- 
mata.     Hutchinson4  has  met  with  similar  cases  of  the  concomitancy  of 
mammary  cancer  with  rodent  ulcer  of  face. 

Bryant 5  and  Michelsohn 6  have  seen  scirrhous  cancer  of  the  breast, 
concomitant  with  epidermoidal  cancer  of  the  nose  (three  cases)  ;  and  the 
former  has  met  with  cancer  of  the  breast  associated  with  cesophageal 
epithelioma. 

Panas  7  mentions  the  case  of  a  man  with  scirrhous  cancer  of  the  breast, 
from  whose  lower  lip  epithelioma  had  been  excised  fifteen  years  pre- 
viously ;  and  similar  cases  have  been  recorded  by  Young  and  Wini- 
warter  ;  while  Graviller  8  has  seen  cancer  of  the  male  breast,  concomitant 
with  epidermoidal  cancer  of  the  lower  lip. 

A  patient  of  Dobson's,9  who  had  remained  well  and  free  from  any 
return  of  the  disease  for  six  years  after  amputation  of  the  breast  for 
cancer,  then  developed  epidermoidal  cancer  of  the  tongue,  of  which  she 
soon  died  ;  another  patient  of  the  same  surgeon,  two  years  after  extirpa- 
tion of  the  breast  for  cancer,  of  which  there  was  no  return,  died  of  small 
round-celled  sarcoma  of  the  tonsil. 

Gibson 10  has  recorded  the  case  of  an  old  woman,  who  died  of  cancer 
of  the  pylorus,  more  than  twenty  years  after  extirpation  of  the  right 
breast  for  cancer  ;  Poulsen's  patient  died  of  cancer  of  the  stomach,  five 
years  after  extirpation  of  the  breast  for  the  same  disease  ;  Nicholls  u  has 
described  cancer  of  the  pyloric  mucosa,  with  acinous  glandular  cancer  of 
the  mamma  ;  and  Fraenkel 12  acinous  cancer  of  the  left  mamma,  with 
cylinder-celled  cancer  of  the  colon. 

Guende 13  met  with  sarcoma  of  the  choroid  in  a  woman,  the  subject  of 
mammary  cancer  ;  Nehrkorn 14  sarcoma  of  the  vagina,  with  mammary 
cancer  ;  and  Schael 15  scirrhus  of  the  mamma,  with  spindle-celled  sarcoma 
of  one  ovary. 

I  have  elsewhere 18  cited  instances  of  associated  mammary  and  ovarian 
cancer  ;  Cutler 17  has  met  with  cancer  of  various  thoracic  and  abdominal 

1  Arch.  Gen.  de  Med.,  April  21,  1903.  2  Chapter  VII. 

3  My  book  on  "  Diseases  of  the  Breast,"  1894,  p.  304. 
*  Archives  of  Surgery,  vol.  iii.,  No.  9,  p.  147. 

6  "  Diseases  of  the  Breast,"  1887,  p.  340.  6  Inaug.  Diss.,  Berlin,  1889. 

7  Cited  by  Poirier,  "  Tumeurs  du  sein  chez  1'horame,"  Paris,  1883,  p.  98. 

8  Canadian  Medical  and  Surgical  Journal,  Montreal,  1873,  p.  271. 

9  Bristol  Med.-Chir.  Journal,  December,  1889.  to  Lancet,  1896,  vol.  ii.,  p.  225. 

II  Montreil  Medical  Journal,  1903,  vol.  xxxii.,  p.  326. 
12  Munch,  med.  Woch.,  1901. 

*3  Marseille  Med.,  1890,  No.  7,  p.  326.  14  Munch,  med.  Woch.,  1901. 

16  Cited  by  Wells  (Journal  of  Pathology  and  Bacteriology,  June,  1901). 
18  "  Diseases  of  the  Breast,"  1894,  p.  306. 

17  Boston  Medical  and  Surgical  Journal,  1892,  p.  329. 

20 


306  THE  NATURAL  HISTORY  OF  CANCER 

organs,  with  sarcoma  of  the  ovary ;  and  Kesteven l  found  that  cancer  of 
the  rectum  and  sarcoma  of  the  femur  developed  in  a  patient,  from  whom 
recurrent  mammary  cancer  had  been  extirpated  six  years  previously, 
without  any  local  recurrence. 

Gastro-intestinal  Tract. — Multiple  primary  malignant  growths  are 
met  with  more  frequently  in  this  system,  than  in  any  other  part  of  the 
body,  except  the  skin.  I  have  previously  referred  to  cases  of  multi- 
plicity due  to  auto-implantation  in  this  locality  ;  and  dissemination  is 
another  complication  to  be  weighed,  in  estimating  the  validity  of  claims 
to  initial  multiplicity. 

Instances  of  this  kind  have  been  reported  as  occurring  in  all  parts  of 
this  tract,  from  the  lips  to  the  anus. 

As  examples,  the  following  may  be  mentioned  : — triple  epidermoidal 
cancer  of  the  tongue  (Hayward  and  Henderson  2)  ;  epithelioma  of  tongue, 
with  sarcoma  of  epiglottis  (Schiller  3)  ;  double  cancer  of  the  oesophagus 
(Bucher  4) ;  epidermoidal  cancer  of  the  tongue,  with  double  cancer  of  the 
oesophagus  (Richter 5) ;  round  and  spindle-celled  sarcoma  with  epider- 
moidal cancer,  both  of  the  lower  part  of  the  oesophagus  (Frangenheim6) ; 
epidermoidal  cancer  of  the  tongue  with  columnar-celled  (colloid)  cancer 
of  the  jejunum  (Abesser 7)  ;  epidermoidal  cancer  of  the  oesophagus  and 
stomach  (Borst 8)  ;  epidermoidal  cancer  of  the  oesophagus,  with  cylinder- 
celled  cancer  of  the  pyloric  glands  (Rosenbach  9) ;  epidermoidal  cancer  of 
the  oesophagus,  with  cylinder-celled  cancer  of  the  ampulla  of  Vater 
(Courmont 10) ;  cylinder-celled  cancer  of  the  pylorus,  with  colloid  cancer  of 
the  caecum — two  cases  (Orth  and  Beck  n) ;  multiple  cancer  of  the  ileum 
(cases  by  Lubarsch  12  and  Bunting 13) ;  multiple  cancer  of  the  jejunum 
(Notthaft 14)  ;  cancer  of  ileum  and  lower  part  of  the  rectum — both  of 
columnar  type  (Robson  and  Knaggs  15)  ;  multiple  cancer  of  the  large 
intestine  and  rectum  (cases  by  Rutherford,  Teacher  and  Buchanan 16)  ; 
cylinder-celled  cancer  of  the  rectum  and  sigmoid  colon — with  multiple 
polypi  (Morton 17)  ;  cylinder-celled  cancer  of  rectum  and  splenic  flexure  of 
colon — with  multiple  polypi  (Handford 18) ;  cancer  of  the  stomach  and 
colon  (Bucher19)  ;  double  cylinder-celled  cancer  at  opposite  ends  of  the 
rectum,  with  multiple  polypi  (Robson  and  Knaggs  20)  etc. 

The  subjects  of  malignant  disease  of  the  gastro-intestinal  tract,  may 
also  develop  the  malady  independently  in  other  parts  of  the  body,  of 

1  Clinical  Society's  Transactions,  London,  vols.  vi.  and  ix. 

2  Lancet,  1901,  vol.  ii.,  p.  22.  3  Berlin,  klin.  Woch.,  1898. 
4  Ziegler's  Beitr.  z.  path.  Anat.,  Bd.  xiv.,  Heft  i.,  S.  100. 

6  Wien.  klin.  Woch.,  1905,  S.  865.  6  Arch.  f.  path.  Anat.,  1906,  Bd.  184. 

7  Cited  in  Michelsohn's  I.  D.  "  Zur  Multiplicitat  der  primaren  Carcinomen."     Berlin, 
1889. 

8  "  Die  Lehre  von  den  Geschwiilsten,"  1902,  Bd.  ii.,  S.  773. 

9  Arch.  f.  path.  Anat.,  1905,  Bd.  clxxix.,  S.  567. 

10  Lyon  Med.,  April  15, 1894. 

11  Cited  by  Bard  (Arch.  Gen.  de  Med.,  1892,  i.,  p.  541). 

12  Arch.  f.  path.  Anat.,  1888,  Bd.  cxi. 

13  Johns  Hopkins  Hospital  Bulletin,  December,  1904,  p.  389. 

14  Deutsche  med.  Woch.,  October  22,  1896.  »  Lancet,  1905,  vol.  i.,  p.  640. 

16  Transactions  of  the  Pathological  Society,  London,  1905. 

17  Lancet,  1895,  vol.  i.,  p.  1145. 

18  Transactions  of  the  Pathological  Society,  London,  1890,  vol.  xlv.,  p.  133. 

19  Ziegler's  Beitr.  z.  path.  Anat.,  Bd.  xiv.  20  Op.  cit. 


MULTIPLE  PRIMARY  CANCER  307 

which  many  instances  have  been  already  cited  in  this  chapter,  and  to 
these  the  following  may  be  added  : — cylinder-celled  cancer  of  the  mucosa 
of  the  colon  with  epidermoidal  cancer  of  the  vulva  by  Chiari ;  x  cancer  of 
the  pyloric  mucosa  with  epidermoidal  cancer  of  the  skin  of  the  right  ear 
by  Hauser  ; 2  cancer  of  the  colon,  rectum  and  right  adrenal  by  Zimmer- 
mann  ;  3  colloid  cancer  of  the  caecum,  with  epidermoidal  cancer  of  the  soft 
palate  by  Frangenheim  ; 4  adeno-carcinoma  of  colon,  with  malignant 
cystoma  of  left  ovary  by  Richter ; 5  carcinoma  of  stomach,  with  glioma 
of  cerebrum  by  Hansemann  ; 6  cylinder-celled  cancer  of  the  stomach,  with 
spindle-celled  sarcoma  of  one  ovary,  by  Buchnell  and  Hinds  ; 7  cancer  of 
the  stomach  of  "  adenoid  type,"  round-celled  sarcoma  of  the  right  testis, 
with  endothelial  sarcoma  of  the  dura  mater  ;  8  cancer  of  the  stomach  and 
bladder  by  Szumann  ;  9  epidermoidal  cancer  of  the  oesophagus,  with  endo- 
theliomata  of  the  dura  mater  by  Kretz  ; 10  epidermoidal  cancer  of  the 
oasophagus,  with  spindle-celled  sarcoma  of  the  stomach  by  Thierfelder  ;  n 
epidermoidal  cancer  of  the  anus,  with  villous  cancer  of  the  bladder  by 
Nehrkorn  ; 12  columnar-celled  cancer  of  the  rectum,  with  epidermoidal 
cancer  of  the  larynx,  has  also  been  described  by  Butlin.13 

Many  examples  of  concomitant  gastric  and  ovarian  cancer  have  been 
reported  ;  as  also  of  gastric  cancer  with  ovarian  fibro-sarcoma,  endo- 
thelioma  etc.  (Krukenberg's  tumours);  intestinal  cancer  has  also  often  been 
found  associated  with  similar  ovarian  lesions  :  I  have  elsewhere 14  referred 
more  fully  to  cases  of  this  type. 

Instances  of  the  concomitant  association  of  sarcoma  of  the  choroid, 
with  malignant  epithelial  tumours  in  other  parts  of  the  body,  have  been 
described  by  Parsons,15  Fischer  and  Bosc. 

From  such  examples  as  the  foregoing,  which  by  no  means  exhaust  the 
list,  the  following  conclusions  may  be  drawn  : — 

1.  The  fact  of  the  occurrence  of  multiple  outbreaks  of  malignant 
disease  is  thus  clearly  established,  both  for  individual  organs,  for  paired 
organs,  and  for  different  parts  of  the  body. 

2.  It  is  further  established,  that  although  primitively  multiple  malig- 
nant tumours  are  generally  of  the  same  kind  ;  yet,  in  many  instances, 
they  are  generically  different  (e.g.,  epithelioma  and  sarcoma)  :  and  even 
when  the  multiple  growths  are  of  the  same  genus  (e.g.,  epitholioma)  they 
may  be  of  different  varieties  (e.g.,  colloid  cancer  of  one  breast  and  scirrhus 
of  the  other  etc.). 

3.  Multiple  outbreaks  of  malignant  disease  are  probably  less  excep- 
tional than  is  generally  believed,  the  evidence  to  this  effect  being  especially 
strong  in  the  case  of  paired  organs. 

Cited  by  Bard.  2  Arch.  f.  path.  Anat.,  1894.  Bd.  cxxxviii.,  S.  402. 

Canadian  Journal  of  Medical  Sciences,  Toronto,  1882,  vol.  vii.,  p.  390. 
Arch.  f.  path.  Anat.,  1906,  Bd.  clxxxiv.,  S.  201. 

Wien.  klin.  Woch.,  1905,  S.  865.  «  Zeits.  /.  Krebsforsch.,  i.,  p.  3,  S.  183. 

British  MedicalJournal,  1905,  vol.  ii.,  p.  1115. 

Cited  by  Beadles  (Transactions  of  the  Pathological  Society,  London,   1897,  vbl. 
xlvi   .,  p.  236). 

Cited  bv  Bard.  1°  Cited  by  Walter  (Arch.  f.  klin.  Chir.,  Bd.  liii.,  1896,  S.  1). 

Ibid.     "  12  Munch,  med.  Woch.,  1901. 

13  British  Medical  Journal,  1905,  vol.  ii.,  p.  1570. 

14  Chapter  XIX.  15  "  Pathology  of  the  Eye,"  1905,  vol.  ii.,  p.  497. 

20—2 


308  THE  NATURAL  HISTORY  OF  CANCER 

4.  Initial  multiplicity  is  relatively  often  concomitantywith  certain 
structural  derangements,  which  may  be  presumed  to  give  predisposition 
thereto.     These  derangements  comprise  pre-natal  developmental  irregu- 
larities, especially  obvious  in  the  early-life,  bilateral  forms  of  multiplicity  ; 
local  hyperplastic  lesions,  such  as  chronic  seborrhoea,  chronic  eczema, 
lupus,  and  the  effects  of  various  irritants  such  as  soot,  tar,  paraffin  etc., 
especially  obvious  in  cutaneous  manifestations  ;  in  the  gastro-intestinal 
system,  such  lesions  as  multiple  polypi ;  and,  in  the  breast,  the  puerperal 
state.     In  the  uterus,  conditions  of  this  kind  are  less  obvious  ;  but  they 
may,  nevertheless,  exist. 

5.  Taken  in  their  entirety,  these  various  considerations  point  to  some 
*  general  systemic  change,  as  the  predisposing  cause  of  primary 7multi- 

plicity. 

The  Question  of  Mixed  Malignant  Tumours. 

The  question  of  the  existence  of  mixed  malignant  tumours,  that  is  to 
say,  of  tumours  in  which  sarcomatous  and  epitheliomatous  processes  go 
on  concurrently,  is  perhaps  as  yet  hardly  ripe  for  dogmatic  treatment, 
by  reason  of  the  paucity  of  well-recorded  facts  relating  thereto. 

On  a  jyriori  grounds,  however,  no  objection  need  be  raised  to  this 
conception  ;  while  some  significant  facts  can  be  cited  in  its  favour. 
Referring  to  this  matter,  Virchow 1  says  :  "  There  are  true  mixed  forms 
of  sarcoma  and  carcinoma — tumours  of  which  certain  parts  are  sarco- 
matous, while  others  are  carcinomatous." 

In  support  of  this  dictum,  reference  may  be  made  to  several  cases  in 
the  foregoing  list,  in  which  two  different  kinds  of  malignant  growth  were 
found  concurrently  in  certain  organs,  either  as  two  separate  tumours, 
or  more  or  less  fused  into  a  single  tumour  (sarco-epithelioma). 

Thus,  in  Frangenheim's  case,  we  see  at  the  lower  end  of  the  oesophagus 
a  round-  and  spindle-celled  sarcoma,  and  so  closely  contiguous  to  it  as  to 
form  but  a  single  morbid  mass — epidermoidal  cancer. 

Then,  in  the  mamma,  we  have  instances  in  which  the  two  kinds  of 
malignant  disease  are  so  closely  combined,  as  together  to  form  but  a 
single  tumour,  as  in  Heurtaux's  case  of  glandular  cancer  with  ossifying 
and  chondrifying  sarcoma,  which  I  have  elsewhere  2  fully  detailed  ;  more- 
over in  this  case,  the  secondary  growths  reproduced  all  the  peculiarities 
of  the  primary  mixed  tumour. 

In  other  parts  of  the  body  similar  instances  have  been  reported, 
especially  in  connexion  with  the  malignant  tumours  of  infancy  and  early 
life  :  thus,  Kaposi 3  has  described  two  examples  of  "  sarco-carinomatous  " 
tumours  of  the  face  of  girls,  aged  respectively  ten  and  seven  years,  who 
had  suffered  from  earliest  infancy  with  xeroderma  of  the  part ;  and 
Lapointe  and  Lecene  4  the  same  type  of  disease  in  the  right  adrenal  of 
an  infant  nineteen  months  old  etc. 

Maier  5  has  described  a  thyroid  tumour  from  a  woman  aged  forty,  in 

1  "  Die  krankhaften  Geschwiilste,"  1863. 

2  My  book  on  "  Diseases  of  the  Breast,"  p.  170. 

3  Hebra's  "  Skin  Diseases,"  Sydenham  Society's  Translation,  vol.  iii.,  p.  254  ;  and 
vol.  iv.,  p.  222.  *  Butt,  et  Mem.  Soc.  Anat.,  Paris,  November.  1904. 

6     Arch.  f.  path.  Anat.,  1877,  Bd.  Ixx.,  S.  378. 


MULTIPLE  PRIMARY  CANCER  309 

which  ossifying  and  chondrifying  sarcoma  and  carcinoma  were  combined  ; 
and  other  instances  of  thyroid  sarco-carcinoma  have  been  reported  by 
Donati,  Syme,  Schmorl,  Kaufmann,  etc.  ;  while  Wells,1  Loeb,  and  Rum- 
mer 2  have  likewise  met  with  this  combination  in  thyroid  tumours  of  dogs. 

It  is,  however,  in  the  uterus  that  the  most  numerous  and  best  studied 
examples  of  this  kind  of  morbid  growth  have  been  found. 

Some  of  the  cases  to  be  cited  in  this  connexion  have  been  adversely 
criticized  ;  but,  in  my  opinion,  their  validity  has  not  been  impaired. 

I  have  previously  referred  to  the  remarkable  cases  of  Niebergall  and 
Milford,  in  which  two  different  forms  of  malignant  disease  were  present 
in  the  same  uterus,  together  with  various  non-malignant  growths. 

Then  there  is  Montgomery's  case,  in  which  glandular  epithelioma  of 
the  cervix  was  concomitant  with  sarcoma  of  the  corpus. 

In  Keller's3  case,  a  round  and  spindle-celled  polypoid  sarcoma  of 
the  cervix  was  associated  with  glandular  epithelioma  of  the  same  part. 

Emanuel 4  found  a  round-celled,  polypoid  sarcomatous  tumour,  grow- 
ing from  the  wall  of  the  corpus,  concurrently  with  diffuse  glandular 
epithelioma  of  the  mucosa  of  the  same  part. 

In  Abel  and  Landau's  5  case,  glandular  epithelioma  of  the  cervix  was 
associated  with  diffuse  sarcoma  of  the  uterine  mucosa. 

In  Rabl-Riickhardt's  6  patient,  after  a  polypoid,  sarcomatous  tumour 
had  been  spontaneously  expelled  from  the  uterus,  the  mucosa  was  then 
found  to  be  affected  with  diffuse  glandular  cancer.  At  several  points, 
cancerous  glandular  ingrowths  from  the  overlying  diseased  mucosa,  had 
penetrated  into  the  sarcomatous  tumour. 

Franque's  7  three  cases  may  next  be  cited  :  in  the  first  of  these,  round- 
and  myeloid-celled  sarcoma  of  the  mucosa  of  the  corpus,  was  concurrent 
with  glandular  epithelioma  of  the  cervix  ;  in  the  second,  cylinder-celled 
glandular  epithelioma  of  the  corpus  was  present,  together  with  round- 
celled  sarcoma  of  the  adjacent  part  of  the  cervix,  the  two  morbid  growths 
being  quite  distinct,  though  contiguous  ;  and,  in  the  third,  sarcoma  of 
the  uterine  wall  was  concomitant  with  glandular  epithelioma  of  the 
cervix. 

Finally,  mention  may  be  made  of  H.  Spencer's  8  case,  in  which  glan- 
dular epithelioma  of  the  corpus,  was  concurrent  with  small  round-celled 
sarcoma  of  the  same  locality. 

Similar  series  of  cases  have  been  reported  in  connexion  with  the  ovary. 

It  requires  no  great  stretch  of  the  imagination  to  see  how,  from  the 
fusion  of  closely  contiguous  growths  of  different  kinds,  such  as  the  fore- 
going series  reveals,  true  mixed  tumours  may  result,  of  which  an  example  )\ 
has  been  reported  by  Rosenstein 9  in  the  uterus  ;  and,  in  other  parts 
of  the  body,  by  Fletcher,10  Maier,11  Kuhnart 12  and  others. 

Journal  of  Pathology  and  Bacteriology,  1901,  vol.  vii.,  p.  352. 

Bev.  Mid.  de  la  Suisse  Romande,  1898,  t.  viii.,  p.  703. 

Zeits.  f.  Geb.  u.  Gyn.,  1890,  Bd.  xx.,  S.  116.  *  Ibid.,  1896,  Bd.  xxxiv.,  S.  1. 

Arch.  f.  Gyn.,  Bd.  xxxii.,  xxxiv.,  and  xxxv. 

Beitr.  z.  Geb.  u.  Gyn.,  1872,  Bd.  1.,  S.  76. 

Zzits.  f.  Geb.  u.  Gyn.,  1899,  Bd.  xl.,  S.  183. 

8  Transactions  of  the  Pathological  Society,  1906;  also  Lancet,  1905,  vol.  ii.,  p.  1109. 

9  Arch.  f.  path.  Anat.,  1883,  Bd.  xcii.,  S.  191. 

10  Transactions  of  the  Pathological  Society,  London,  1902,  vol.  lii.,  p.  199. 

11  Arch.  f.  path.  Anat.,  Bd.  Ixx.,  S.  378.     "  12  Arch.  f.  Gyn.,  1874,  Bd.  vi. 


310  THE  NATURAL  HISTORY  OF  CANCER 

Although  the  histological  and  some  of  the  general  biological  char- 
acters— especially  the  reproduction  of  the  original  mixed  type  in  the 
disseminative  lesions  of  certain  rare  malignant  growths — seem  to  coun- 
tenance the  belief  in  the  existence  of  mixed  malignant  tumours,  it  must 
not  be  concluded  on  this  account,  that  transitions  from  one  type  of 
malignant  growth  to  another  occur  (transformation,  metaplasia).  Never 
have  transitions  of  this  kind  been  verified.  This  proposition  rests  on  a 
mistaken  apprehension  as  to  the  origin  of  the  tissue  cells,  the  specificity 
of  which  modern  cytological  studies  have  revealed. 

Thus,  among  neoplastic  tissues,  as  among  the  normal  tissues,  there 
are  no  transitions  from  one  specific  type  to  another  ;  in  fact,  the  meta- 
plasia of  Virchow  has  no  real  existence. 


The  Association  of  Malignant  with  Non-malignant  Tumours. 

It  not  uncommonly  happens  that  malignant  and  non- malignant 
tumours  are  associated,  in  the  same  individual,  of  which  some  remarkable 
examples  have  been  cited  above. 

"  In  further  illustration  of  the  subject,  reference  may  be  made  to  the 
case  of  a  woman,  aged  fifty-two,  who  died  after  abdominal  hysterectomy 
for  uterine  myomata,  when  Lubarsch 1  found  sarcoma  of  the  gall-bladder, 
a  large  adenoid  polypus  of  the  stomach,  a  small  "  tumour  "  in  the  spleen, 
lipoma  of  the  right  kidney,  "  struma  suprarenahs  aberrans,"  cystic 
kidneys  and  enchondroma  of  the  right  pleura. 

In  Guy's  Hospital  Museum2  is  a  specimen  of  cancer  of  the  uterus, 
concomitant  with  adenoma  of  the  right  adrenal ;  and  Bosanquet 3  has 
found  cancer  of  the  stomach,  with  adenoma  of  both  adrenals.4 

Lubarsch5  has  met  with  cancer  of  the  stomach,  in  association  with 
multiple  polypi  and  cystic  adenoma  of  the  part ;  and,  many  instances 
of  this  kind  have  been  reported,  in  the  large  intestine.  Maier  6  encoun- 
tered enchondroma  of  the  kidney,  with  cancer  of  the  same  ;  and,  enchon- 
droma of  the  subcutaneous  tissue  of  the  thorax,  also  with  cancer.  ^ 

De  Santi 7  found  fibroma  papillare  of  the  nasal  septum,  with  rodent 
ulcer  of  the  nose. 

Milian 8  epithelioma  of  the  lung  and  cancer  of  the  parotid,  with 
adenomata  of  the  liver. 

Many  instances  of  the  association  of  cancer  of  the  liver  with 
"  adenoma  "  of  the  same,  have  also  been  reported  (Schmieden,9  Wells,10 
Eggel u  etc.) ;  and  in  the  thyroid  this  concomitancy  is  far  from 
uncommon.  ( 

Cited  by  Walter  (Arch.  f.  klin.  Chir.,  1896,  Bd.  liii.,  S.  1). 

No.  2,020,  Pathological  catalogue. 

Transactions  of  the  Pathological  Society,  London,  1902,  vol.  lii.,  p.  64. 

For  other  instances  of  concomitant  adrenal  tumours  and  cancer  elsewhere, '.  vide 


Cha 


pter 

Ar 


IX.  5  Cited  by  Walter. 


Arch.  f.  path.  Anat.   1877,  Bd.  Ixx.,  S.  378. 
Lancet,  December  8,  1894. 

Butt,  et  Mem.  Soc.  Anat.,  Paris.plarch  19,  1897. 
Arch.  f.  path.  Anat.,  1900,  Bd.  clix.,  S.  290. 

10  American  Journal  of  Medical  Science,  1903,  p.  403. 

11  Ziegler's  Beitr.  z.  path.  Anat.,  etc.,  1901,  Bd.  xxx.,  S.  506. 


ASSOCIATION  OF  CANCER  WITH  OTHER  TUMOURS     311 

Smyly l  found  spindle-celled  sarcoma  of  the  lower  end  of  the  femur, 
concomitant  with  a  large  ossified  enchondroma,  and  a  lipoma,  all  of  the 
same  vicinity. 

Uterine  myomata  are  often  present  in  the  cancerous  as  in  the  non- 
cancerous  ;  thus,  of  79  necropsies  for  uterine  cancer  in  my  list,  myomata 
were  present  in  5  or  in  6-3  per  cent.,  and  in  many  cases  mucosal  polypi 
as  well.  11-3  per  cent,  of  my  breast  cancer  cases,  were  subject  to  uterine 
myomata.  As  mentioned  in  the  preceding  chapter,  in  cancer  of  other 
localities,  uterine  myomata  coexisted  in  18-5  per  cent,  of  the  necropsies. 

Tate  2  has  seen  cylinder-celled  epithelioma  of  the  corpus  uteri  con- 
comitant with  myomata  of  the  same,  and  with  myoma  of  the  left  ovary  ; 
Cullen  3  found  cancer  of  the  corpus  uteri,  with  multiple  uterine  myomata, 
and  papillary  cystoma  of  both  ovaries. 

According  to  Chiari,4  the  subjects  of  uterine  myoma  are  unduly 
prone  to  cancer.  Of  25  women  with  myomata  under  his  observation, 
2  had  cancer  of  the  uterus,  1  cancer  of  the  breast,  and  6  had  cancer  of 
other  organs.  This  is  a  very  slender  basis  on  which  to  rest  such  a 
sweeping  statement.  If  Chiari's  views  were  correct,  we  should  expect 
to  find  uterine  myomata  much  more  frequently  in  the  cancerous  than  in 
the  non-cancerous.  But,  of  159  female  cancer  necropsies  in  my  list, 
uterine  myomata  were  present  in  only  20,  or  in  12-5  per  cent.  ;  whereas, 
according  to  Bayle,  they  are  found  in  20  per  cent,  of  all  women  over 
thirty-five.  Hence  Chiari's  conclusion  must  be  rejected. 

In  like  manner  ovarian  cystomata — oophoronic,  parovarian  and 
dermoid — are  fairly  often  found  in  association  with  malignant  tumours  : 
thus,  of  Lebert's  45  uterine  cancer  necropsies,  ovarian  cystomata  were 
present  in  3  ;  and,  of  Winckel's  numerous  cases  of  ovarian  cystomata, 
8  per  cent,  had  also  uterine  cancer. 

Of  44  necropsies  for  mammary  cancer  in  my  list,  ovarian  cystomata 
were  present  in  3. 

The  association  of  ovarian  cystomata  with  malignant  disease  of  other 
parts  of  the  body,  especially  of  the  gastro-intestinal  tract,  is  also  an 
occurrence  of  no  great  rarity.5 

Of  85  female  mammary  cancer  patients  in  my  list,  fatty  tumours  were 
present  in  2 ;  one  of  these  patients  was  also  the  subject  of  multiple 
molluscum  fibrosum,  an  ovarian  dermoid,  and  a  mucous  polypus  of  the 
cervix  uteri. 

De  Morgan  and  Murchison  have  each  seen  uterine  cancer,  associated 
with  multiple  lipomata  of  various  parts  of  the  body. 

1  Transactions  of  the  International  Medical  Congress,  London,  1881,  vol.  i.,  p.  114 
(specimen  exhibited  in  museum). 

2  Transactions  of  the  Obstetrical  Society,  London,  1905,  vol.  xlvi.,  p.  138. 

3  "  Cancer  of  the  Uterus,"  1901,  p.  463. 

4  "  Klin,  der  Geburts.,"  etc.    Erlangen,  1853. 

5  Lockyer  (Practitioner,  November,   1903),  case  of  cancer  of  rectum  with  ovarian 
cystomata  ;  and  Terrier  (  Union  Med.,  Paris,  1887,  t.  xliv.,  p.  5),  sarcoma  of  transverse 
colon,  with  cystoma  of  right  ovary.     Deanesly  (British  Medical  Journal,  1902,  vol.  i., 
p.  1148)  and  Boucher  (New  York  Medical  Secord,  1902,  November  22,  p.  816),  cases  of 
cancer  of  colon,  with  bilateral  ovarian  cystoma,  etc. 


CHAPTER  XIV 


THE  INFLUENCE  OF  SEX 

THE  influence  of  sex  in  determining  the  localization  and  incidence  of 
tumours  is  very  great ;  and,  it  is  noteworthy,  that  both  malignant  and 
non-malignant  varieties  are  subject  thereto.  This  seems  to  imply,  that 
the  conditions  determining  the  growth  of  both  varieties  of  tumours  are 
the  same  in  kind,  and  differ  only  in  degree. 

In  illustration  of  the  subject,  reference  may  be  made  to  my  analysis 
of  15,481  primary  tumours  of  all  kinds,  consecutively  under  treatment 
at  four  large  metropolitan  hospitals,  during  a  period  of  from  sixteen  to 
twenty-one  years,  as  follows  : — 

TABLE  SHOWING  THE  SEX  INCIDENCE  OF  15,481  PRIMARY  TUMOURS. 


Total. 

Males. 

Females. 

Sex  Ratio. 

Epithelioina  —  i.e.,      malignant     epithelial 
tumours 

7878 

2861 

5017 

1  to  1'75 

Sarcoma 

1350 

702 

648 

1  „  0'92 

Non-malignant  tumours 

4613 

1179     i     3434 

1   „  2'91 

Cysts              

1640 

449     !     1191 

1  „  2'65 

15,481 

5,191 

10,290 

1  „  T98 

The  greater  prevalence  of  malignant  epithelial  tumours  among  females, 
is  entirely  due  to  the  frequency  with  which  the  mammae  and  uterus  are 
affected,  the  corresponding  structures  in  males  very  rarely  originating 
the  disease  l ;  while,  in  nearly  every  other  locality,  the  male  liability 
preponderates,  as  I  have  elsewhere  pointed  out.2 

Hence  sarcomatous  tumours,  which  do  not  manifest  this  special  pro- 
clivity to  attack  the  female  reproductive  organs,  are  more  equally  dis- 
tributed between  the  sexes. 

My  analysis  also  shows,  that  the  relative  proneness  of  females  to 
non-malignant  tumours  and  cysts,  is  even  greater  than  it  is  to  malignant 
epithelial  tumours  ;  and,  as  a  detailed  examination  of  the  matter  indi- 
cates, this  is  attributable  to  the  undue  frequency  with  which  in  women 
the  uterus  and  ovaries  are  attacked,  the  corresponding  male  organs 
seldom  being  affected  by  tumours  of  this  type. 

An  inference  from  the  foregoing  is,  that  we  must  seek  for  an  explana- 

1  The  national  mortality  returns,  for  1900,  show  that  the  female  cancer  death-rate- 
less  the  mortality  due  to  cancer  of  the  mammary  and   generative  organs — was  583  per 
million,  as  against  660,  the  corresponding  male  rate. 

2  Chapter  XVII. 

312 


THE  INFLUENCE  OF  SEX  313 

tion  of  these  remarkable  diversities  in  morbid  proclivity,  in  biological 
peculiarities  inherent  to  the  affected  parts,  and  in  their  concomitant 
developmental  and  structural  diversities — all  of  which  are  ultimately 
ascribable  to  functional  modifications — rather  than  to  any  general  con- 
stitutional condition  correlated  with  sex.  As  mentioned  in  a  previous 
chapter,  the  greater  proclivity  of  human  females  to  cancer,  than  the 
females  of  animals,  is  due  rather  to  circumstances  connected  with  the 
special  sheltered  environment  of  the  former,  than  to  any  peculiarity 
connected  directly  with  sex.  It  accords  with  this  that  of  late — when 
owing  to  urbanization  the  conditions  of  existence  for  men  and  women 
have  been  rendered  less  divergent — the  disparity  in  cancer  proclivity  has 
lessened,  and  this  change  is  still  in  progress.  Of  like  import  is  the  great 
frequency  of  cancer  in  castrated  animals  of  both  sexes,  to  which  I  have  " 
previously  referred.1 

We  may  also  turn  for  information  as  to  the  influence  of  sex  in  malig- 
nant disease,  to  the  national  mortality  returns. 

Thus,  the  Sixty-third  Report  of  the  Registrar-General,  for  the  year 
1900,  shows  that  among  males  the  cancer  mortality  was  672  per  million 
living  of  that  sex,  the  corresponding  figure  for  females  being  975  :  in  the 
same  year  26,721  persons  died  of  the  disease,  of  whom  10,475  were  males 
and  16,246  females — the  sex  ratio  being  1  male  to  1-5  females  ;  1  male 
died  of  cancer  to  every  29  male  deaths  from  all  causes,  and  1  female  died 
of  this  disease  to  every  17  female  deaths  ;  and  finally,  of  persons  aged 
thirty-five  years  and  upwards,  1  in  15  men  and  1  in  9  women  died  of 
cancer. 

For  the  year  1906,  the  respective  cancer  death-rates  were  794  per 
million  for  males,  and  1,032  for  females,  the  sex  ratio  being  1  male  to 
1-3  females. 

As  I  have  elsewhere  shown,2  this  increasing  cancer  mortality  has 
affected  males,  to  a  much  greater  extent  than  females.  In  further  illus- 
tration of  this  subject,  the  foregoing  data  may 'be  compared  with  those 
derived  from  the  massed  national  mortality  returns  for  the  twenty-five 
years  1848-1872,  which  show  a  sex  ratio  of  1  male  to  2-29  females  ; 
1  male  having  died  of  cancer  to  every  100  male  deaths,  and  1  female  to 
every  41  female  deaths. 

It  seems  likely,  if  the  disproportionate  increase  of  cancer  among  males, 
now  going  on  in  our  country,  continues  unchecked,  that  the  disease  will 
eventually  become  more  prevalent  among  men  than  among  women,  as 
is  already  the  case  in  Australia  and  New  Zealand  ;  thus,  in  1900,  the 
cancer  death-rate  for  all  Australia  was  591  for  males,  as  against  only 
550  for  females,  and  this  excess  of  male  cancer  mortality  has  been 
apparent  ever  since  1870. 

In  the  United  States,  and  in  such  European  countries  as  publish 
national  mortality  returns,  the  sex  incidence — in  its  main  features — is 
similar  to  that  of  our  country.  Thus,  of  29,475  cancer  deaths  in  the 
United  States,  during  1900,  11,436  were  males  and  18,039  females,  the 
sex  ratio  being  1  to  1-5. 

From  these  data  it  may  be  concluded  that,  while  the  female  liability 
1  Chapter  V.  and  VII.  2  Chapter  III. 


314  THE  NATURAL  HISTORY  OF  CANCER 

to  cancer  in  nearly  all  modern  communities,  still  much  exceeds  the  liability 
of  males  ;  yet,  this  disparity  in  sex  incidence,  is  tending  rapidly  to  dis- 
appear. As  I  have  previously  mentioned,  this  may  be  accounted  for  as 
the  result  of  the  changed  conditions  of  modern  life  which  predispose  to 
cancer,  pressing  with  disproportionate  severity  on  men. 

The  information  derivable  from  crude  national  mortality  returns  is 
valuable,  chiefly  on  account  of  the  massif  of  the  totals,  which  tend  to 
mitigate  the  disturbing  influence  of  the  many  defects  inherent  to  such 
compilations.  It  is,  however,  easier  to  point  out  flaws  of  this  kind,  than 
to  remedy  them  ;  for,  with  almost  every  "  correction,"  new  sources  of 
error  are  necessarily  introduced,  so  that  the  indications  furnished  by 
the  crude  returns  are  often  more  reliable,  as  resting  on  a  broader  basis. 
than  those  furnished  by  "  corrected  "  data. 

Modern  statisticians  sometimes  forget,  that  compilations  of  this  kind 
are  necessarily  unsuited  by  their  very  nature  for  the  discrimination  of 
fine  details  ;  it  is  rather  for  furnishing  reliable  general  indications,  that 
these  monumental  works  are  so  valuable. 

In  drawing  conclusions  as  to  the  relative  frequency  of  cancer  in  the 
two  sexes,  from  the  crude  mortality  sex  ratios,  it  is  evident  that  allowance 
should  be  made  for  the  fact,  that  in  most  of  the  countries  concerned,  the 
sexes  are  unequally  represented  in  the  general  population,  females  pre- 
ponderating. This,  of  course,  tends  to  minimize  the  disparity  revealed 
by  the  crude  ratios  ;  although  the  disturbing  factor  in  this  case  is  not 
sufficiently  potent,  to  change  the  character  of  the  general  result. 

Even  by  comparing  the  respective  cancer  death-rates  of  males  and 

females,  we  are  unable  exactly  to  discriminate  the  relative  liability  of 

the  sexes  ;  because,  the  frequency  of  cancer  varies  at  different  ages,  and 

the  age  distribution  of  an  equal  number  of  both  sexes  is  also  very  different, 

>-  women  living  to  a  greater  age  than  men  etc. 

As  a  corrective  to  disturbing  influences  of  this  kind,  the  cancer 
mortality  may  be  calculated  separately  for  those  of  each  sex  above  a 
certain  age,  say  thirty-five  years  old  and  upwards,  of  which  I  have 
previously  given  the  results  for  our  country. 

But  even  such  a  comparatively  perfect  method  as  this,  fails  to  quite 
satisfy  some  statistical  experts.  Laspeyres I  proposes  to  solve  the  problem 
by  calculating  separately  the  mortality  of  each  sex,  at  each  of  the  various 
age-periods,  insisting  that  the  mortality  of  each  sex  varies  greatly  accord- 
ing to  age  :  thus,  during  the  age-period  thirty  to  fifty  years,  he  finds  that 
the  cancer  mortality  of  women  is  much  greater  than  that  of  men  ;  2  while, 
from  fifty  to  seventy  and  upwards,  the  male  mortality  is  the  greater. 
De  Bovis3  proposes  to  attain  the  same  end,  by  placing  side  by  side  100,000 
of  each  sex,  arranged  according  to  their  respective  age  distribution  ;  and 
then  calculating  by  age,  the  number  of  cancer  deaths  that  each  of  these 
totals  will  produce.  These  results  being  derived  from  male  and  female 
populations  ide  tical  in  their  number  and  composition,  readily  furnish 
the  required  sex  ratios,  when  the  corresponding  numbers  are  compared. 

1  Cent.  f.  attg.  Gesundheitspflege,  1901,  S.  342. 

2  This  result  is  mainly  due  to  the  precocity  of  uterine  and  mammary  cancer. 

3  La  Semaine  Mid.,  Xo.  37,  1902. 


THE  INFLUENCE  OF  SEX 


315 


Applying  this  method  to.  our  population,  aged  twenty-five  and  upwards, 
he  finds  that  the  relative  liability  of  the  sexes  to  cancer  is  100  males  to 
139  females  ;  in  Holland,  the  corresponding  ratio  is  100  to  123  ;  in  Prussia, 
100  to  101  ;  while  for  Norway,  it  is  100  males  to  87  females  ;  and  in 
Switzerland,  100  to  88. 

The  localization  of  malignant  and  other  tumours  is  also  much  influ- 
enced by  sex,  as  is  well  illustrated  by  the  tabular  statements  given  in 
another  chapter.1  As  the  national  mortality  returns  show,  in  70-6  per 
cent,  of  the  cancer  deaths  among  males,  the  disease  is  situated  in  the 
alimentary  system  (stomach  21-4)  ;  among  females,  the  corresponding 
percentage  is  43-3  (stomach  13-2).  Uterine  (23-5)  and  mammary  (15-8) 
forms  of  the  malady,  account  for  39-3  per  cent,  of  the  total  female  cancer 
mortality. 

The  hospital  returns  analysed  by  me  show,  that  68-6  per  cent,  of  all 
malignant  epithelial  tumours,  among  males,  were  located  in  the  alimen- 
tary system,  the  corresponding  percentage  for  females  being  15-2  :  among 
females,  74-3  per  cent,  of  these  tumours  were  situated  in  the  breast  (40-3) 
and  uterus  (34). 

No  such  striking  sex  diversities  in  localization  are  noticeable  among 
the  sarcomata,  as  the  figures  in  my  analysis  show  ;  and  of  1,789  sarcomata 
tabulated  in  the  national  mortality  returns  (1903),  860  were  in  females 
and  929  in  males. 

The  following  data  by  Dr.  Tatham,  which  are  based  on  the  national 
mortality  returns  for  1897-1900  (comprising  in  all  102,685  deaths  from 
cancer),  further  illustrate  this  subject. 

TABLE  SHOWING  THE  SEX  INCIDENCE  OF  CANCER  IN  RELATION  TO 
LOCALIZATION. 


Deaths. 

Death-rates  per  Million 
Living. 

Localization. 

Males. 

Females. 

Males. 

Females. 

Uterus,  mamma,  and  repro- 

ductive organs 

726 

25,151 

12 

384     / 

Stomach 

8369 

8355 

136 

127  fr 

Intestine 

6312 

6731 

103 

103 

Liver 

5532 

8654 

90 

132 

(Esophagus 
Tongue 

2358 
2124 

852 
271 

38 
35 

13 
4 

Throat 

891 

334 

15 

5 

Lip 

647 

74 

11 

1 

Mouth 

508 

115 

8 

2 

All  parts        

40,317 

62,368 

657 

952 

The  age  incidence  of  cancer  is  considerably  earlier  in  women  than  in 
men,  owing  to  the  precocity  of  the  uterine,  mammary  and  ovarian  forms 
of  the  disease  ;  thus,  according  to  Karl  Pearson,  the  mean  age  of  2,368 
female  cancer  patients  was  48-8  years,  as  against  53-3  years  for  632  male 
patients.  Pearson  also  finds  that  the  age  incidence  of  cancer  in  man,  is 
more  variable  than  in  women. 

1  Chapter  XVIII. 


316 


THE  NATURAL  HISTORY  OF  CANCER 


I  have  found  the  mean  age,  at  onset,  of  the  chief  local  forms  of  malig- 
nant epithelial  tumours,  to  be  as  follows  :— for  females,  uterus  44,  mamma 
4s,  stomach  47-4,  rectum^  50-5,  skin  50,  oesophagus  50-6,  tongue  and 
mouthJtiO,  rodent  ulcer  42-5  ^tc.  ;  and  for  males,  stomachal- 1,  tongue 
and  mouth  53-8,  lower  lip  52-4,  rectum  49-7,  oesophagus  56,  skin  52-4, 
^  mamma  50,  rodent  ulcer  48-8  etc.1 

The  following  tabular  statement  from  the  Registrar- General's  Reports, 
indicates  the  mean  annual  mortality  from  cancer  per  million  living  of 
each'sex,  at  successive  age-periods,  during  the  decennia  1851-1860  and 
1891-1900  respectively. 

TABLE  SHOWING  THE  CANCER  DEATH-RATES  OF  EACH  SEX,  AT  SUCCESSIVE 
AGE-PERIODS,  DURING  THE  DECENNIA  1851-1860  AND  1891-1900. 


AGE-PERIODS. 

MALES. 

FEMALES. 

1851-1860. 

1891-1900. 

1851-1860.     1891-1900. 

All  ages. 

195 

600 

434 

906 

Under  5  years 

21 

33 

23 

28 

5  t. 

o  10 

10 

18 

9 

14 

10  , 

,  15 

8 

19 

9 

14 

15 

20 

16 

32 

18 

27 

20 

25 

27 

51 

30 

39 

25 

35 

63 

99 

141 

175 

35 

45 

174 

384 

592 

891 

45 

55 

422 

1300 

1278 

2323 

55 

65 

931 

3160 

1853 

4099 

65 

75 

1504 

5325 

2350 

5829 

Over  75 

1749 

5824 

2341 

6377 

These  data  clearly  indicate  the  very  much  higher  mortality  of  females, 
than  of  males,  at  aU  age-periods  after  the  twenty- fifth  year  ;  and  they 
also  show  the  rapid  rise  of  mortality  for  both  sexes,  in  the  age-periods 
succeeding  the  twenty-fifth  year.  It  is  noteworthy  in  this  connexion, 
that  the  female  mortality  shows  much  greater  augmentation  than  the 
male  mortality,  both  in  the  aggregate,  and  at '  each  successive  age- 
period  after  the  twenty-fifth  year.  The  influence  of  sex  in  relation  to 
age  incidence  is,  indeed,  most  marked  between  the  twenty-fifth  and 
fifty-fifth  years. 

In  infancy,  childhood  and  early  life,  prior  to  the  twenty-fifth  year, 
there  is  no  such  marked  difference  in  morbid  proclivity  ;  for,  most  of  the 
tumours  of  this  early  period  being  sarcomatous,  the  sex  incidence  is 
approximately  equal,  with  however  a  distinct  bias  in  favour  of  males. 

1  According  to  Lebert  ("Traite  des  mal.  canceruses,"  1851),  the  average  age  at  onset  of 
the  chief  forms  of  cancer  then  was  as  follows  :  uterus  44,  tongue  47,  mamma  50,  stomach 
54,  bladder  55,  intestine  55,  skin  57,  liver  57,  and  oesophagus  60  years  :  the  mean  age 
for  all  cancer,  he  estimated  at  about  51  years.  Sibley  (Transactions  of  the  Med.-Chir. 
Society,  London,  1859,  vol.  xlii.)  gives  43'38  as  the  average  age  of  uterine -cancer  patients  ; 
48'6  for  mammary,  and  55'3  for  lip  cancer  in  males.  Xunn  ("Cancer  of  the  Breast." 
1882)  estimates  the  average  age  of  uterine  cancer  at  45'7,  and  of  mammary  at  50'4. 
From  these  figures  it  may  be  inferred  that  there  has  been  no  marked  alteration  in  the 
age  incidence  of  cancer  during  the  last  half-century. 


CHAPTER  XV 
THE  INFLUENCE  OF  AGE 

IN  order  to  appreciate  the  influence  of  age  in  the  aetiology  of  malignant 
tumours — the  great  importance  of  which  I  have  strongly  insisted  on  in 
all  my  publications 1 — it  is  necessary  to  be  accurately  acquainted  with 
the  actual  facts  as  to  the  age  distribution  of  this  particular  malady  ;  and 
also  to  have  some  knowledge  as  to  the  role  of  age,  with  regard  to  mor- 
tality in  general. 

The  best  source  of  information  as  to  the  incidence  of  malignant  disease 
in  general,  at  the  various  age-periods,  is  to  be  found  in  the  national 
mortality  returns.  The  subjoined  table,  from  the  Sixty-third  Report  of 
the  Registrar-General,  shows  the  age  distribution  of  the  deaths  from  this 
cause  in  England  and  Wales,  during  the  year  1900,  as  follows  : — 


TABLE  I. 

SHOWING  THE  AGE  DISTRIBUTION  OF  CANCER  MORTALITY  IN  EACH 
SEX  DURING  1900. 


11 

5- 

10- 

15- 

20- 

25- 

35- 

45- 

55- 

i 
65-    i    75- 

If 

All 
Ages. 

aog- 

Males 

61 

21 

36 

47 

83 

235 

748 

1942 

3245 

2832    1095 

HO 

10,475 

Females 

58 

38 

32 

53 

73 

502 

1803 

3539 

4509 

3799    1641  |  f99    16,246 

From  these  data  we  learn  the  absolute  frequency  of  the  mortality  at 
the  various  age-periods,  the  maximum  being  attained  for  both  sexes, 
during  the  decennium  fifty-five  to  sixty-five.  It  will  be  noted  that 
95  per  cent,  of  the  total  deaths  occur  after  the  thirty-fifth  year,  and 
86  per  cent,  after  the  forty-fifth  year.2  These  data  tell  us  very  little 
as  to  the  relative  tendency  of  each  sex  to  cancer,  at  different  periods. 
In  order  to  ascertain  this,  we  must  compare  the  figures  with  the  total 
number  of  each  sex  living,  at  the  corresponding  age-periods.  The  fol- 
lowing table,  which  has  been  compiled  on  this  basis,  shows  the  mean 
cancer  mortality,  per  million  living  of  each  sex,  in  groups  of  ages,  for  the 
year  1900. 


1  "  Twentieth  Century  Practice  of  Medicine,"  1898,  vol.  xvii.,  pp.  241,  487  ; 
of  the  Breast,  with  Special  Keference  to  Cancer."  1894,  p.  238 ;  "Uterine  Tumours,"  1901, 
p.  242  ;  and  "  The  Principles  of  Cancer  and  Tumour  Formation,"  1888. 

a  In  marked  contrast  with  the  above,  76  per  cent,  of  all  deaths  from  phthisis  occur 
prior  to  the  forty -fifth  year. 


318 


THE  NATURAL  HISTORY  OF  CANCER 


TABLE  II. 

SHOWING  THE  CANCER  DEATH-RATES  IN  EACH  SEX,  AT  DIFFERENT 
AGE-PERIODS.  FOR  1900. 


II 

5- 

10- 

15- 

20- 

25-         35- 

45- 

55- 

65- 

11 

All 
Ages. 

v> 

3    I 

Males 

31 

11 

20 

29 

60 

101      418 

1483 

3796 

5735 

6715 

672 

Females 

29 

20 

18  j  32 

47 

197      942 

2433 

4561 

6254 

7468 

975 

From  these  sources,  as  well  as  from  the  data  given  at  the  end  of  the 
preceding  chapter,  we  learn  that  cancer  begins  to  be  frequent — in  both 
sexes — after  the  twenty-fifth  year  ;  and  that  the  relative  mortality  from 
it  increases  rapidly  and  progressively,  with  eacli  successive  decade,  until 
the  seventy-fifth  year,  females  being  in  this  respect  much  more  pre- 
cocious than  males  from  the  start,  as  is  specially  noticeable  in  the  age- 
period  forty-five  to  fifty-five. 

Dr.  Bashford1  regards  this  progressive  age  distribution  as  "specially 
characteristic  "  of  cancer,  but  this  is  a  mistake  ;  for,  a  similar  tendency 
is  noticeable  with  regard  to  mortality  from  most  diseases,  e.g.,  diseases 
of  the  urinary,  respiratory  and  nervous  systems,  diabetes  etc.  Indeed, 
the  liability  of  the  cancer  mortality  to  increase  with  age,  as  compared 
with  the  corresponding  liability  to  death  generally,  shows  undue  rapidity 
of  augmentation  up  to  the  decennium  forty-five  to  fifty-five  ;  but,  after 
this  period,  the  general  mortality  increases  far  more  rapidly  than  the 
cancer  mortality.  Referring  to  this  subject,  Dr.  Ogle  remarks2:  "In 
simply  saying  that  the  liability  to  death  from  cancer  increases  with  age, 
no  more  is  said  than  may  be  stated  with  equal  truth  of  liability  to  death 
generally.  The  question  is,  Does  the  annual  liability  to  death  from 
cancer  increase  more  rapidly  than  the  annual  liability  to  death  of  all 
kinds  ?"  To  answer  this  query,  he  has  compiled  the  following  table, 
showing  the  ratio  of  total  deaths  from  cancer  during  the  .decennium 
1871-1880,  at  successive  age-periods. 


TABLE  HI. 

SHOWING  THE  TOTAL  DEATHS  TO  ONE  FROM  CANCER  AT  SUCCESSIVE 
AGE-PERIODS 


Age-Periods.                                        Persons. 

•Males. 

Females. 

20  to  25  years 

i\  255 

262 

248 

25  „  35      , 

71 

131 

49 

35  „  45      , 

24 

57 

15 

45  „  55      , 

14 

28 

9 

55  „  65      , 

22 

10 

65  „  75      , 

21 

27 

17 

75  and  upwards 

1           48 

56 

44 

1  Scientific  Report  of  the  Imperial  Cancer  Research  Fund,  1905,  No.  2,  pt.  1. 

2  Forty-seventh  Annual  Report  of  the  Registrar-General  for  England  and  Wales. 


THE  INFLUENCE  OF  AGE  319 

As  will  be  gathered  from  the  above,  the  characteristic  feature  of  the 
cancer  mortality  is,  not  its  progressive  increase  with  advance  of  years — 
for  this  it  shares  with  most  other  lethal  maladies — but  its  dispropor- 
tionate augmentation  in  the  post-meridian  periods — i.e.,  forty-five  to 
sixty-five. 

The  above  table  also  shows  well,  the  relative  liability  of  the  sexes  at 
different  ages.  It  will  be  noticed  that  the  proclivity  of  females  increases 
until  the  decennium  forty-five  to  fifty-five,  when  it  attains  its  maximum, 
after  which  it  lessens  progressively  at  each  decade  in  a  marked  degree  : 
on  the  other  hand,  the  male  maximum  is  not  attained  until  a  later  period, 
viz.,  the  decennium  fifty-five  to  sixty-five,  corresponding  with  the  slower 
decline  of  reproductive  activity  in  the  male  sex. 

With  regard  to  cancer  of  the  female  breast,  statistics  compiled  on 
this  principle  by  Paget  1  and  Nunn,2  show  that  the  period  of  its  greatest 
relative  frequency  is  between  the  fortieth  and  fiftieth  years.  Nunn's 
table,  which  was  compiled  for  him  by  an  actuary,  is  as  follows  : — 

TABLE  IV. 

SHOWING  THE  RELATIVE  FREQUENCY  OF  MAMMARY  CANCER  AT  THE 
DIFFERENT  AGE-PERIODS. 


Ag 

2.-)  t 

:jo 
.-55 
40 
4."> 
50 
.->-) 
(i() 
60 
70 
16 
80 

j-Periods 
o  30  ye 
,  35 
,  40 
,  45 
,  50 
,  55 
,  60 
,  65 
,  70 

Per  Cent, 
ars                                                                           "831 

3-933 

,                                                                             8'783 

12'311 

18-006 
16-161 
8'368 

9'696 

9'181 

,  75 

,  80 
,  85 

4'983 

3-923 
3-824 

lOO'OOO 

This  shows  that  the  relative  liability  of  women  to  mammary  cancel- 
lessens  progressively,  in  a  marked  degree,  at  each  age-period  after  fifty- 
five. 

Considerations  of  this  kind  induced  me  to  investigate  the  mortality 
from  cancer  of  centenarians,  and  of  aged  persons  of  eighty  years  upwards. 
The  information  thus  obtained  shows,  that  these  aged  persons  are  rela- 
tively much  less  prone  to  the  disease  than  their  juniors.  Cancer  seldom 
originates  in  extreme  old  age.  Thus,  of  1,087  centenarians,  of  whom  the 
causes  of  death  are  tabulated  in  the  Registrar-General's  Reports  for  the 
fifteen  years  1871-1885,  only  5  died  of  cancer,  or  1  in  217  ;  of  the  295 
males,  2  died  of  cancer,  or  1  in  147  ;  and  of  the  792  females,  3  died  of  it, 
or  1  in  264. 

The  localization  of  the  disease  in  these  centenarians  is  stated  in  only 
one  case,  this  patient  being  a  woman,  who  died  aged  106,  of  ''  cancer  of 
the  eye  and  wrist." 

1  "  Lectures  on  Surgical  Pathology,"  1853,  vol.  ii.,  p.  326. 

2  "  Cancer  of  the  Breast,"  1882,  p.  161. 


320  THE  NATURAL  HISTORY  OF  CANCER 

Humphry's  report l  on  the  maladies  of  old  people,  is  of  similar  import. 
Thus,  among  202  persons  (males  92,  females  110),  ninety  years  of  age 
and  upwards,  there  was  not  a  single  instance  of  malignant  disease  ;  and, 
of  622  persons  (males  340,  females  282),  between  eighty  and  ninety  years 
old,  there  were  only  14  instances  of  it.  Thus,  of  these  824  aged  persons, 
malignant  disease  was  met  with  only  in  1-7  per  cent,  of  the  total  cases, 
or  in  the  ratio  of  1  to  58-8.  Of  432  males,  7  were  cancerous,  or  1  in  61-7  ; 
and  of  392  females,  7  were  similarly  affected,  or  1  in  56.  Of  the  males, 
the  lip  was  the  seat  of  the  disease  in  3  cases  ;  the  penis,  ear,  finger  and 
shoulder,  each  in  1  case.  Of  the  females,  in  5  the  mamma  was  the  part 
affected,  and  in  2  the  face. 

These  facts  clearly  show  that  cancer  is  not  a  senile  disease  ;  and  that 
X  senility,  per  se,  plays  no  part  in  its  development. 

The  contrary  belief,  which  has  lately  been  advocated  in  influential 
quarters,  is  the  outcome  of  misunderstanding  of  the  facts  ;  and  especially 
of  failure  to  appreciate  "  age  incidence,"  in  respect  to  mortality  in 
general,  as  I  have  above  indicated. 

Thus,  the  special  feature  in  the  age  incidence  of  malignant  disease  is, 
its  connexion  with  decline  in  reproductive  activity  ;  and  not  in  its  fancied 
relation  to  senility. 

In  animals,  as  in  mankind,  the  maximum  incidence  of  cancer  like- 
wise coincides  with  decline  in  reproductive  activity,  rather  than  with 
senility  per.  se,  as  I  have  previously  had  occasion  to  indicate.2 

In  the  preceding  chapter,  some  reference  was  made  to  the  influence 
of  sex,  in  respect  to  the  localization  of  malignant  tumours. 

In  further  elucidation  of  this  subject,  I  now  submit  the  subjoined 
table,  showing  the  absolute  frequency  of  the  malady  in  the  chief  sites,  at 
different  age-periods,  in  each  sex,  the  data  being  derived  from  the  national 
mortality  reports  for  the  three  years  1901-1903  (see  Table  V.,  p.  321). 

From  these  figures  the  corresponding  death-rates  may  be  calculated, 
by  employing  the  usual  formula.3 

It  should  be  borne  in  mind  that  the  figures  refer  to  the  age 
incidence  at  death  ;  and  not  to  the  first  obvious  manifestation  of  the 
disease.  Even  so,  however,  they  clearly  indicate  the  precocity  of  the 
uterine,  ovarian,  and  mammary  forms  of  the  disease  in  women  :  in  both 
sexes,  gastric,  hepatic  and  rectal  cancers  occupy  an  intermediate  position 
in  respect  to  age  incidence  ;  while,  lingual,  intestinal,  cesophageal  and 
cutaneous  manifestations  are  of  late  occurrence,  in  both  sexes. 

Hospital  mortality  statistics  give  similar  results. 

For  some  of  the  chief  local  manifestations  of  malignant  epithelial 
tumours,  I  have  compiled  the  following  data,  showing  the  age  at  the 
onset  of  the  first  obvious  symptoms  of 'the  disease,  among  hospital  patients 
(see  Table  VI.,  p.  322). 

The  general  import  of  these  data  is  to  diminish  the  sharpness  of  the 
diversities  in  age  incidence,  revealed  by  the  mortality  returns  ;  which 
are  thus  seen  to  be  due,  to  a  considerable  extent,  to  differences  in  the 
duration  of  life  of  the  various  local  forms  of  the  disease.  In  estimating 

1  British  Medical  Journal,  July  30,  1887.  2  Chapter  V. 

For  details,  vide  Sixty-sixth  Annual  Report  of  the  Registrar-General  for  1903. 


THE  INFLUENCE  OF  AGE 


321 


the  influence  of  age,  in  this  connexion,  it  is  necessary  not  to  lose  sight 
of  this  important  consideration. 

A  curious  feature  revealed  by  careful  study  of  age  incidence,  in 
relation  to  uterine  malignant  epithelial  growths  is,  lhat  this  malady 
originates  in  the  corpus,  at  a  much  later  period  than  in  the  cervix. 


TABLE  V. 

SHOWING  THE  AGE  AND  SEX  INCIDENCE  OF  MALIGNANT  TUMOURS  IN 
RESPECT  TO  LOCALIZATION,  BASED  ON  THE  NATIONAL  MORTALITY 
RETURNS  1901-1903. 


MALES. 

Localization. 

Under 
25 

Years. 

25-     35- 

45- 

55- 

65- 

75- 

85  and  up- 
wards. 

Total. 

Stomach 

13 

116 

527 

1374 

2390 

2168 

728    33 

7349 

Liver  and  gall- 

bladder .  . 

42 

61 

287 

817 

1471 

1362 

511 

45 

4596 

Rectum 

26 

86 

210 

614 

1060 

918 

404 

32 

3350 

Tongue  and 

mouth  .  . 

9 

17 

176 

593 

844 

618 

225    20 

2501 

Intestines  .  . 

22 

64 

169 

412 

711 

723 

267    17 

2385 

(Esophagus  .  . 

1 

8 

125 

504 

752 

524 

185     8 

2107 

Skin 

15 

20 

58 

155 

280 

408 

365 

89 

1390 

Bladder  and 

urethra  .  . 

9 

10     45 

164 

273 

379 

171    17 

1068 

Jaw 

28 

9  !   71 

215 

314 

267 

107     1 

1012 

All  other  sites 

539  |  367    760 

1580 

2179 

1860 

681    64 

8030 

Totals 

704    758 

2428 

6427 

10,274 

9227 

3644   326 

33,788 

FEMALES. 

Uterus 

20 

518 

2094 

3472 

3061 

1861 

620 

68 

11,714 

Mamma 

4 

179 

1040 

2112 

2209 

1682 

952 

189 

8367 

Stomach  .  . 

'  7 

107 

503 

1289 

2135 

2167 

839 

72 

7119 

Liver  and  gall- 
bladder.. 

32 

77 

418 

1173 

2168 

2111 

882 

74 

6935 

Intestines  .  . 

19 

71 

227 

584 

945 

1005 

444 

43 

3338 

Rectum 

17 

100 

236 

553 

834 

793 

372 

34 

2939 

Ovary 

30 

72 

168 

276 

222 

126 

24 

2 

920 

Abdomen  .  . 

20 

17 

47 

179 

235 

269 

108 

13 

888 

Peritoneum  .  . 

10 

28 

74 

147 

273 

223 

76 

9 

840 

(Esophagus  .  . 
Skin 

1 
6 

37 

10 

79 
32 

140 

67 

164 

110 

207 
173 

92 
189 

5 

50 

725 
637 

Tongue  and 

mouth  .  . 

6 

22 

31 

48 

83 

122 

54 

4 

370 

All  other  sites 

422 

266 

630 

1093 

1410 

1323 

616 

108 

5868 

Totals  .. 

594 

1504 

5579 

11,133 

13,849 

12,062 

5268 

671 

50,660 

According  to  Hofmeier,  the  average  age  of  patients  thus  affected  at  the 
onset  of  the  disease  is  54-5  years,  or  over  ten  years  later  than  the  age  at  X 
which  cancer  of  the  cervix  supervenes. 

As  the  subjoined  analysis  of  the  age  incidence  shows,  most  cases  of 
this  local  variety  of  the  disease,  arise  during  the  decennium  fifty  to  sixty 

21 


322 


THE  NATURAL  HISTORY  OF  CANCER 


(51  per  cent.)  ;  whereas,  with  epithelioma  of  the  cervix,  the  period  of 
maximum  frequency  is  the  decennium  thirty-five  to  forty-five  (37  per 
cent.). 

In  illustration  of  this,  I  have  made  the  following  analysis  showing 
the  age  incidence  of  epithelioma  of  the  corpus  uteri,  in  100  cases  reported 
by  Pichot,  Gusserow,  J.  Williams  and  myself,  as  follows : — twenty  to  thirty 
years,  in  8-3  cases  ;  thirty  to  forty,  in  3-6  ;  forty  to  fifty,  in  19  ;  fifty  to 
sixty,  in  51-2 ;  sixty  to  seventy,  in  16-7  ;  and,  at  over  seventy  years,  in 
1-2  cases. 

Although  many  pathologists  even  now  regard  the  sarcomata  as  a 
form  of  malignant  disease,  chiefly  -met  with  in  quite  young  persons,  yet, 

TABLE  VI. 

SHOWING  THE  AGE  AND  SEX   INCIDENCE   OF  EPITHELIOMA  IN  RESPECT 
TO  LOCALIZATION,  BASED  ON  THE  AGE  AT  ONSET. 


MALES. 

Under 

75  and 

Localization. 

25 

25- 

35- 

45- 

55- 

65-         up- 

Total. 

Aver. 

Max. 

Min. 

Years. 

1 

wards. 

Stomach 

2 

4 

9 

20 

16 

7 

1 

59 

51-1 

76 

19-25 

Tongue        and 

mouth 



1 

19 

38 

32 

9 

1 

100 

53-8  |  78'5 

25'6 

Lower  lip 



8 

17 

34 

27 

13 

1 

100 

52-4     75-5 

26 

Rectum 

4 

8 

18 

22 

20 

11 



83 

49'7     74 

16'75 

Mamma 

2 

11 

23 

32 

19 

12 

1 

100 

50        82 

20 

Skin 

— 

7 

13 

19 

19 

7 

3 

68 

52'4    85'25 

27 

"Rodent  ulcer" 

— 

4 

5 

4 

7 

2 

— 

22 

48'5    70 

26 

FEMALES. 

Uterus  (cervix) 
Mamma 

0-2 
0-6 

18 
10 

37 
30 

29 
35 

14 
19 

I, 

0-8      %  on  500 
%  on  500 

44 

48 

83 
84 

22-25 
24 

Rectum 

3 

9 

9 

15 

23 

6 

66 

5Q-4 

88 

21-8 

Tongue        and 

mouth 

3 

12 

14 

39 

19 

12 

%  on  90 

50 

77-5 

24 

Stomach 



5 

11 

10 

7 

2 

36 

47-4 

81 

25-75 

Skin        .... 



7 

11 

10 

8 

6 

43 

50 

75-5 

26 

"Rodent  ulcer" 

2 

2 

8 

6 

2 

1 

— 

21 

42-5 

66 

14 

several  years  ago,  I  pointed  out  that  this  was  a  mistake  ;  and  that  the 
"^sarcomata,  like  the  epitheliomata,  become  progressively  more  frequent 
with  advancing  years. 

I  then  expressed  myself  as  follows  : 1  "  The  sarcomata  may  arise  at 

any  period  of  life  :  a  certain  number  of  cases  are  congenital ;  more  are 

-.    met  with  in  early  infancy,  especially  during  the  first  five  years,  than  at 

any  period  prior  to  the  twentieth  year  ;  after  which  sarcomata  increase 

in  frequency  until  middle  life,  becoming  rarer  again  in  old  age."     Thus, 

there  is  a  certain  general  resemblance  in  the  age  incidence  of  the  two 

types  of  malignant  disease  ;  whence  also  may  be  inferred  a  certain  setio- 

logical  kinship,  to  which  I  specially  directed  attention,  in  these  words  : 

1  "  Twentieth  Century  Practice  of  Medicine,"  1898,  vol.  xvii.,  p.  487. 


THE  INFLUENCE  OF  AGE 


323 


"  It  will  be  gathered  from  what  has  been  stated,  that  there  are  close 
analogies  between  the  two  diseases — sarcoma  and  carcinoma — such 
differences  as  are  noticeable  being  due  to  diversity  of  origin  and  its  con- 
sequences, rather  than  to  any  essential  difference  in  the  nature  of  the 
morbid  process." 

Nearly  all  of  the  malignant  tumours  of  early  life  are  sarcomata  ; 
malignant  epithelial  tumours  are,  at  this  period,  of  exceedingly  rare 
occurrence  :  thus,  of  941  malignant  tumours  consecutively  under  my 
observation,  806  were  of  the  epithelial  type  and  136  sarcomatous  ;  in 
only  1  of  the  former  did  the  disease  originate  under  twenty  years  of  age, 
whereas  the  latter  furnished  24  cases.  It  is  just  at  these  early 
periods  of  life,  that  the  age  incidence  of  the  two  types  of  malignant 
disease  is  so  different. 

The  following  analysis  of  consecutive  hospital  cases  tabulated  by  me, 
based  on  the  age  at  the  onset  of  the  malady,  makes  this  very  clear  :— 

TABLE  VII. 

SHOWING  THE  AGE  INCIDENCE,  AT  ONSET,  OF  SARCOMA  IN  BOTH  SEXES. 


SB' 

•§•8  I 

f,J 

5- 

10- 

1ft. 

20- 

25- 

35- 

45- 

55- 

65- 

§  *  j  Total. 

Aver. 

Max. 

Min. 

10 

ejj 

Males 

2 

2 

6 

6 

7 

22 

10 

20 

16 

8 

i 

100 

40'4 

79 

2 

Females  .  . 

7 

1 

6 

8 

12 

13 

11 

25 

11 

5 

i 

100 

36'7 

78'4 

0'5 

It  is  mainly  owing  to  the  comparative  frequency  of  sarcomata  during 
early  life,  that  the  average  age  of  sarcoma  patients,  at  the  onset  of  the 
malady,  is  more  than  ten  years  earlier  than  the  corresponding  averages 
for  those  with  malignant  epithelial  tumours  ;  and,  to  the  same  cause, 
may  be  ascribed  the  greater  precocity  of  the  disease  in  female  than  in 
male  sarcomatous  patients,  as  displayed  in  the  above  table. 

The  national  mortality  returns  for  the  year  1903,  supply  the  following 
information  on  this  subject,  based  on  1,789  cases. 

TABLE  VIII. 

SHOWING  THE  AGE  DISTRIBUTION,  AT  DEATH,  OF  SARCOMA 


II 

ft. 

10- 

15- 

20- 

25- 

35- 

45- 

55- 

65- 

75- 

li 

«& 

Total. 

a 

Males 

58 

33 

21 

38 

42 

93 

138 

169 

183 

107 

44 

3 

929 

Females 

36 

24 

18 

33 

34 

80 

110 

171 

178 

123 

45 

8 

860 

The  differences  between  these  mortality  data,  and  those  based  on  the 
age  at  onset  of  the  malady,  may  be  mainly  attributed  to  the  relatively 
long  duration  of  life,  in  a  large  proportion  of  the  sarcoma  patients. 

Here  I  take  the  opportunity  of  pointing  out,  that  the  age  incidence  of 
that  interesting  malady  "  chorio-epithelioma  "  vel  "deciduomamalignum," 
the  precise  nosological  status  of  which  has  yet  to  be  determined,  is  far 

21—2 


324 


THE  NATURAL  HISTORY  OF  CANCER 


more  akin  toTtheJconnective-tissue  type  of  malignant  tumour  than  to 
the  epithelial'type  ;  and,  in  a  subsequent  chapter1  I  shall  show  that  the 
indications  derived  from  study  of  its  local,  lymph-gland,  and  general 
dissemination  are  of  similar  import. 

Considerations  of  this  kind  ought  not  to  be  neglected,  in  determining 
the  nosological  status  of  this  somewhat  anomalous  and  newly-described 
malignant  growth  :  they  are  probably  more  reliable  than  the  conclusions 
derived  merely  from  histogenesis,  which  make  this  way  and  that  way, 
according  to  the  prepossession  of  the  moment,  this  part  of  the  subject 
still  being  involved  in  great  obscurity,  notwithstanding  the  dogmatic 
assertions  of  the  predominant  authorities,  who  appear  to  me  to  have  based 
their  present  conception  too  exclusively  on  the  histological  appearances. 

Teacher's  analysis  2  of  170  cases  shows  that  the  average  age  of  those 
affected  with  this  malady  was  thirty-three  years  :  the  decennial  incidence 
was  as  follows  : — 

Age-Periods.  Cases. 

17  to  20  years  . .          . .  .  in     6 


In  twenty-two  cases,  the  patients  were  over  forty-five  years  old. 

Since  malignant  epithelial  tumours  are  hardly  ever  met  with  under 
the  age  of  twenty,  it  may  be  concluded  that  nearly  all  the  early-life 
malignant  tumours,  tabulated  in  the  national  mortality  returns,  belong 
to  the  sarcomata. 

The  following  table,  compiled  from  data  supplied  by  the  Registrar- 
General's  Annual  Reports,  shows  the  age  incidence  of  sarcoma  in  early 
life,  for  both  sexes,  during  the  latter  half  of  the  nineteenth  century,  and 
some  other  interesting  particulars  : 

TABLE  IX. 

SHOWING  THE  DEATH-RATES  FROM  MALIGNANT  TUMOURS  IN  EARLY 
LIFE,  PER  MILLION  PERSONS  LIVING,  FROM  1851-1860  TO  1891-1900. 


MALES. 

Age-Periods. 

Under  5 
Years. 

5- 

10- 

15- 

20- 

All 
Ages. 

1851-1860 
1861-1870 

21 
13 

10 

8 

8 

7 

16 
18 

27 
26 

195 
242 

1871-1880       
1881-1890       
1891-1900 

13 
21 
33 

7 
11 
18 

8 
12 
19 

16 
23 
32 

27 
37 
51 

312 
430 
600 

FEMALES. 

1851-1860 
1861-1870       
1871-1880       
1881-1890       
1891-1900       

23 
13 
12 
19 

28 

9 
7 
7 
9 
14 

9 

7 
7 
1     10 
14 

18 
16 
14 
18 

27 

30 
32 
36 
33 
39 

434 
519 
617 
739 
906 

Chapter  XIX.  2   British  Journal  o[  Obstetrics  and  Gynaecology,  1900,  vol.  iv. 


THE  INFLUENCE  OF  AGE  325 

This  table  shows  that  there  has  been  considerable  increase  in  the 
mortality  from  malignant  tumours,  at  these  early  periods,  during  the 
last  two  decennia  of  the  nineteenth  century  ;  and,  as  at  later  periods, 
both  sexes  participated  in  this  augmentation — which,  however,  affected 
males  more  than  females. 


Congenital  and  Early-Life  Tumours. 

Less  than  half  a  century  ago  Virchow  wrote  :  *  :'  Hardly  any  cases 
of  congenital  sarcoma  are  known."  Since  then,  vast  additions  have  been 
made  to  our  knowledge  of  the  malignant  tumours  of  early  life  ;  and 
hundreds  of  cases  of  congenital  malignant  disease  have  been  reported. 
A  large  proportion  of  these  early-occurring  malignant  tumours  are  un- 
doubtedly congenital ;  that  is  to  say,  they  originate  during  pre-natal  life. 
Unfortunately,  most  of  the  records  of  these  acquisitions  are  still  buried 
in  the  archives  of  learned  societies,  where  they  are  beyond  the  ken  of 
practitioners  ;  hence,  even  in  treatises  dealing  specially  with  the  diseases 
of  children,  little  or  nothing  is  to  be  found  on  this  important  subject. 
To  remedy  this  deficiency,  some  years  ago  I  unearthed  and  analysed  a 
large  number  of  these  remarkable  cases,  2  which  have  great  significance 
for  the  correct  appreciation  of  the  aetiology  of  malignant  disease  in  general, 
although  the  important  indications  thus  furnished  are  still  generally 
overlooked  by  pathologists. 

In  the  course  of  this  undertaking,  I  was  specially  impressed  with  the 
large  proportion  of  these  early-life  malignant  tumours,  that  obviously 
arise  in  connexion  with  pre-natal  developmental  irregularities ;  indeed, 
so  many  tumours  of  this  kind  are  undoubtedly  of  congenital  origin,  that  it 
seems  not  unreasonable  to  assume  a  pre-natal  origin  for  the  whole  group. 
^  I  thus  became  convinced,  that  tumour  genesis  is  intimately  con- 
nected with  teratology — the  stone  which  the  builders  of  modern  "  tumour 
science  "  have  so  unwisely  rejected. 

As  to  the  comparative  frequency  of  the  occurrence  of  pre-natal 
tumours,  we  have  very  little  precise  information ;  for,  the  bodies  of 
infants  have  never  been  systematically  submitted  to  post-mortem 
examination^with  this  end  in  view,  especially  those  of  the  prematurely 
born  and  the  still-born. 

Another  noteworthy  feature  about  the  tumours  of  infancy  and  early 
life  is,  that  the  localities  whence  they  are  prone  to  originate,  are  very  v 
different  from  those  whence  malignant  tumours  commonly  arise  at  later 
periods  of  life. 

Thus,  Duzan's  3  analysis  of  the  records  of  182  malignant  tumours  in 
early  infancy,  shows  the  following  localization  of  the  malady  :  eye  in 
70  cases,  kidney  45,  testis  11,  prostate  8,  bones  5,  tongue  5,  brain  5, 
abdomen  5,  lung  4,  dura  mater  4,  pancreas  3,  liver  2,  tonsil  2,  rectum  2,> 
the  stomach  in^l  case  etc. 

According  to  the  larger  analysis  of  Picot,4  which  embraces  424  cases, 

1  Die  krankhaften  Oeschwukte,  Bd.  ii.,  S.  239.         2  Lancet,  1897,  vol.  i.,  p.  1194  et  seq. 

3  "  Du  Cancer  chez  les  Enfants,"  These  de  Paris,  1876. 

4  "  Les  Tumeurs  malignes  des  Enfants,"  JRev.  Med.  de  la  Suisse  romande.  1883. 


326  THE  NATURAL  HISTORY  OF  CANCER 

the  initial  seats  of  the  disease  were  as  follows,  in  order  of  relative  fre- 
quency :  —  eye  and  its  annexes  in  100  cases,  kidney  in  80,  bones  in  67, 
brain  and  its  membranes  in  31  (dura  mater  6),  abdomen  and  pelvis  in 
19,  testis  in  15,  liver  in  13,  prostate  in  8,  skin  in  8,  intestine  in  7,  neck, 
tongue  and  ovary,  each  in  6  cases  etc. 

The  relation  of  localization  to  age  incidence  in  the  malignant  tumours 
of  early  life,  is  shown  by  the  following  analysis  of  56  consecutive  cases 
under  my  own  observation  :  of  these,  14  originated  in  the  first  quin- 
quenniad  viz.,  in  the  eye  7  cases,  kidney  2,  testis,  inferior  maxilla,  base 
of  skull,  sacro-coccygeal  region  and  tibia,  each  in  one  case  ;  in  the  second 
quinquenniad  6  cases  originated  viz.,  in  the  liver,  parotid,  kidney,  tibia, 
cervical  lymph-gland,  and  inferior  turbinated  bone,  each  in  1  case  ;  the 
third  quinquenniad  furnished  16  cases  viz.,  in  the  inferior  maxilla  4, 
femur  3,  fibula  3,  tibia,  humerus,  acromion  process  of  scapula,  parotid, 
thigh  muscles,  external  ear,  and  retina,  each  1  case  ;  in  the  fourth  quin- 
quenniad 20  cases  arose  viz.,  in  the  femur  4,  superior  maxilla  3,  inferior 
maxilla  3,  lymph-glands  2,  testis,  pharynx,  kidney,  parotid,  base  of 
skull,  humerus,  orbit  and  subcutaneous  connective-tissue  of  the  back, 
of  each  1  case. 

The  great  proclivity  of  infants  to  malignant  disease  of  the  kidney, 
stands  in  remarkable  contrast  with  the  extreme  rarity  of  this  kind  of 
malady  at  later  periods  of  life  (only  32  cases  in  8,378  primary  malignant 
tumours). 

Then,  retinal  gliomata  are  peculiar  to  early  infancy,  being  rare  after 
the  fifth  year,  and  after  puberty  they  hardly  ever  arise  ;  and,  of  eight  cases 
within  my  own  experience,  in  four  the  disease  was  of  congenital  origin. 

The  scapula  is  remarkable  among  the  skeletal  bones,  for  the  early 

.'    age  at  which  malignant  tumours  originate  from  it,  and  for  their  frequency  ; 

thus,  of  25  bone  sarcomata  in  young  infants,  tabulated  by  Poinsot,1  in 

11  the  scapula  was  the  part  affected,  and  congenital  cases  have  been 

met  with. 

In  contrast  with  this  proclivity  of  the  scapula  to  malignant  tumours 
in  early  infancy,  the  long  bones  are  rarely  affected  in  this  way,  until  the 
ohird  quinquenniad,  when  a  large  number  of  cases  arise  :  thus,  of  Gross'  2 
147  cases,  only  3  arose  during  the  first  quinquenniad,  and  3  during  the 
second  ;  whereas  45  cases  originated  between  the  ages  of  ten  and  twenty 
years  :  similarly,  of  119  cases  tabulated  by  Butlin  and  Colby,3  only  3 
belong  to  the  first  quinquenniad  and  3  to  the  second  ;  whereas,  35  origi- 
nated between  the  ages  of  ten  and  twenty  years. 

These  examples  of  extreme  diversity  in  age  incidence,  according  to 
localization,  suffice  to  show  the  futility  of  attempts  to  illustrate  the  age 
incidence  of  sarcoma  in  general,  by  calculating  the  death-rates  at  different 
age-periods  on  the  basis  of  certain  selected  sites,  after  the  manner  adopted 
by  Bashford  ;  4  for,  supposing  renal  or  retinal  cases  to  predominate  in 
such  selections,  the  death-rate  for  the  period  of  infancy  would  thus  be 
inflated  out  of  due  proportion  etc. 

1  Rev.  de  CUr.,  1885,  t.  v.,  p.  201. 

2  American  Journal  of  the.  Medical  Sciences,  July.  1879,  p.  24. 


3  Bartholomew's  Hospital  Reports,  1895,  p.  31. 

4  Scientific  Report  of  the  Imperial  Cancer  Rese 


Research  Fund,  1905,  part  i.,  Xo.  2,  p.  30 


THE  INFLUENCE  OF  AGE  327 

We  are  now  in  a  position  to  discuss  the  interesting  question,  as  to  the 
earliest  age  at  which  malignant  epithelial  tumours  may  occur. 

In  this  connexion,  it  must  be  remembered  that  the  sharp  distinction 
now  made  between  epithelioma  and  sarcoma,  is  of  comparatively  recent 
origin.  Many  instances  of  congenital  and  early-life  malignant  tumours, 
containing  epithelial  elements,  have  been  met  with,  especially  in  the 
renal,  testicular,  ovarian,  gastric,  hepatic  and  intestinal  regions  ;  and, 
such  tumours  have  often  been  described  as  epitheliomata.  With  regard 
to  such  cases,  it  seems  probable  that  the  contained  epithelial  elements 
play  but  a  secondary  part ;  and  that  all  tumours  of  this  kind  really  are 
sarcomatous. 

In  other  examples  of  alleged  epithelioma  in  early  life,  the  diagnosis 
has  been  based  too  exclusively  on  the  microscopical  appearances,  the 
clinical  features  of  malignancy  being  conspicuous  by  their  absence. 
Instances  of  this  kind  have  been  published  in  connexion  with  the  skin, 
lips,  tongue,  external  genitalia  etc. 

In  short,  I  conclude  that  pre-natal  life,  infancy  and  childhood,  are  X 
completely  exempt  from  malignant  epithelial  tumours. 

The  earliest  age  at  which  epithelioma  has  been  satisfactorily  demon- 
strated is  eleven  years,  the  patient  being  a  girl  with  cylinder-celled  cancer 
of  the  rectum  ; 1  and  I  have  myself  met  with  rodent  ulcer  in  a  young 
woman,  in  whom  the  disease  began  at  the  early  age  of  fourteen  years.2 

In  spite  of  a  few  exceptional  cases  of  this  kind,  it  may  be  safely 
asserted  that,  under  the  age  of  puberty,  cancer  is  practically  unknown. 

In  further  illustration  of  these  remarks,  I  propose  briefly  to  discuss 
the  available  evidence,  in  relation  to  such  representative  localizations  as 
the  rectum,  stomach,  uterus  and  mamma. 

The  rectum  is  remarkable  for  the  comparatively  large  number  of 
malignant  epithelial  tumours,  that  arise  from  it  during  early  life.  More- 
over, as  previously  mentioned,  the  earliest  duly  authenticated  example 
of  epithelioma  hitherto  recorded,  has  been  met  with  in  this  situation. 
The  number  of  cases  of  rectal  epithelioma — in  which  the  disease  originated 
under  twenty  years  of  age — that  might  be  cited,  is  considerable. 

The  following  examples  of  which  I  have  cognizance  will  suffice  to 
illustrate  this  :  two  cases  of  columnar  epithelioma  in  boys  twelve  years 
old,  by  Milne  3  (colloid)  and  Allingham ; 4  at  thirteen,  by  Czerny  5  (boy) 
and  Michaux ; 6  at  fifteen,  by  Godin ; 7  at  sixteen,  by  Lazarus- 
Barlow  ;  8  at  seventeen,  cases  by  Schoening,9  Cripps 10  and  others.  At 
later  periods,  under  twenty,  the  recorded  cases  are  so  numerous  as  to 
render  detailed  references  unnecessary. 

In  early  life,  malignant  tumours  of  any  part  of  the  gastro-intestinal 
tract  are  of  great  rarity  :  thus,  of  2,000  necropsies  on  children  analysed  by 

1  Stern,  Deutsche  med.  Woch.,  1892,  No.  22. 

2  British  Medical  Journal,  1890,  vol.  ii.,  p.  895.  3  Ibid.,  1905,  vol.  ii.,  p.  925. 
4  "  Diseases  of  the  Rectum."  4th  edit.,  p.  270. 

6  Munch,  med.   Woch.,  March  17,  1896,  No.  11. 

6  Transactions  of  the  Academy  of  Medicine  of  Richmond,  Virginia,  U.S.,  July  8, 
1890.  7  Cited  in  Molliere's  "  Traite  des  Maladies  du  Rectum,"  etc. 

8  Archives  of  Middlesex  Hospital.  1904,  vol.  ii. 

9  Deutsche  Zeits.  f.  Chir.,  1885,  Bd.  xxii.,  Heft  1  and  2. 
10  Lancet,  1884,  vol.  ii.,  p.  67. 


328  THE  NATURAL  HISTORY  OF  CANCER 

Steiner  and  Neureutter,  not  a  single  instance  of  malignant  disease  of  the 
stomach  was  met  with.  Some  idea  of  the  extreme  infrequency  of  gastric 
epithelioma  at  this  period,  may  be  gathered  from  the  fact,  that  of  2,075 
cases  tabulated  by  Welch,  only  2  originated  under  the  age  of  twenty 
years. 

However,  several  alleged  examples  of  this  kind  have  been  reported 
in  infancy  ;  and  2  cases  are  said  to  have  been  congenital. 

Congenital  hypertrophy  of  the  pylorus — not  a  very  rare  condition 
judging  from  the  numerous  cases  lately  recorded — has  often  been  mis- 
taken for  infantile  malignant  disease,  as  in  cases  reported  by  Williamson  * 
and  others  ;  and  thus  most  of  these  anomalous  tumours  may  be  explained. 

Congenital  adenomata  are  occasionally  found  in  the  stomach,  as  in 
cases  reported  by  Hueter,  Schmorl  and  others.  These  growths  are  of 
innocent  nature  ;  but  they  occasionally  originate  sarcomatous  disease. 
Kuhn2  has  described  a  case  of  this  kind,  in  a  female  infant  two  yeais 
old,  as  "  adenoid  cylinder-celled  cancer."  A  commoner  occurrence  is 
for  inflamed  tumours  of  this  kind  to  be  mistaken  for  malignant  disease, 
as  in  Culling wor th' s 8  case  of  so-called  congenital  epithelioma  of  the 
pylorus.  Ashby  and  Wright's4  case  of  "  columnar  epithelioma  "  of  the 
pylorus  etc.,  in  a  child  eight  years  old,  seems  to  me  to  belong  to  the  same 
category. 

The  earliest  duly  authenticated  example  of  a  malignant  epithelial 
tumour  of  the  stomach,  is  N.  Moore's  case  ; 5  the  patient  being  a  girl 
thirteen  years  old,  who  died  cachectic,  with  a  large  tumour  projecting  into 
the  stomach,  which  grew  from  the  gastric  wall  near  the  cesophageal  orifice, 
and  histologically  proved  to  be  "  alveolar  cancer." 

Other  instances  of  gastric  epithelioma,  in  the  second  decade,  have 
been  reported  by  Scheffer  6  (pylorus)  at  fourteen,  by  Jackson  7  at  fifteen, 
by  Lidner  and  Kuttner8  at  sixteen,  by  Koster,9  Landouzy,10  Hirtz,11 
Boas  ^  and  others  at  seventeen,  by  Aiming 13  at  nineteen  etc. 

Under  the  age  of  twenty,  malignant  epithelial  tumours  of  the  uterus 
are  hardly  ever  met  with  ;  and  they  are  unknown  prior  to  puberty. 

Of  500  consecutive  cases  in  my  list,  the  earliest  age  at  onset  was 
twenty-two  and  a  quarter  years.  By  massing  the  statistics  of  several 
Continental  and  English  authors,  Gusserow  obtained  a  total  of  3,385 
cases  ;  and  of  this  large  number,  only  2  originated  under  twenty. 

The  earliest  age  at  which  the  outbreak  of  uterine  epithelioma  has 
been  duly  substantiated,  is  seventeen  years  ;  Schauta14  and  Glatter15  have 
each  recorded  an  instance  of  this  kind — the  cervix  being  the  seat  of  the 
disease,  which  was  glandular  epithelioma. 

1  London}and  Edinburgh  Monthly  Journal  of  the  Medical  Sciences,  1841,  vol.  i.,  p.  23. 
-  Berlin,  klin.  Woch.,  1886,  No.  27. 
3  British  MedicalJournal,  1877,  vol.  ii.,  p.  203. 
"  Diseases  of  Children,"  1905,  5th  edit.,  p.  118. 

5  Transactions  of  the  Pathological  Society,  London,  1885,  vol.  xxxvi.,  p.  195. 

6  Jahrb.  f.  Kinder  keilkunde,  1880,  Bd.  xv.,  S.  425. 

7  Cited  by  Osier.  "  Cancer  of  Stomach,"  1900,  p.  19. 

8  Cent.  f.  d.  Grenzgebiete  d.  Med.  u,  Chir.,  Bd.  i.,  Nr.  12. 

9  Cent.  f.  Chir.,  1888,  S.  372.  10  BuU.  de  la  Soc.  Anal,  de  Paris,  1872,  p.  27. 

11  La  Med.  Moderne,  July  26,  1896. 

12  Cited  by  Osier,  "  Cancer  of  the  Stomach,"  1900,  p.  19. 

*3  Lancet,  1902,  vol.  ii.,  p.  1386.  14   Wien.  klin.  Woch.,  1880,  Nos.  37  and  38. 

16  Deutsche  Vierteljahresschrift  f .  off.  Gesundheitspftege,  1870,  Bd.  ii.,  S.  161. 


THE  INFLUENCE  OF  AGE  329 

Munde l  and  Spinelli 2  have  reported  cases  at  eighteen ;  Beigel,3 
Eckhardt 4  and  Tschop  5  have  each  met  with  the  disease  at  nineteen,  and 
Billroth  6  at  twenty. 

Several  instances  of  so-called  cancer  of  the  uterus,  at  much  earlier 
periods,  have  been  recorded  ;  but,  in  none  of  them  has  the  cancerous 
nature  of  the  affection,  been  satisfactorily  established. 

•,  In  Ganghofner's  7  case  of  so-called  cancer  of  the  portio,  in  a  girl  only 
nine  years  old,  the  eroded  papillary  outgrowth  was  more  like  a  non- 
malignant  "  cauliflower  excrescence  " — of  which  several  instances  have 
been  met  with  in  infancy  and  childhood — than  cancer.  The  clinical 
history  accords  with  this  ;  for,  although  the  disease  was  of  over  two 
years'  duration,  it  was  localize  .  ;  and  there  was  complete  absence  of 
dissemination. 

The  instances  of  so-called  cancer  of  the  uterus  by  Heckford  at  nine 
months,  by  Rosenstein  at  two  years,  by  Laidley  at  two  and  a  half  years, 
by  Barnes  at  ten,  by  Simpson  at  twelve,  and  by  Zweifel  at  thirteen  years, 
were  evidently  sarcomatous. 

The  first  four  quinquennia  of  life  are  completely  exempt  from  malig- 
nant epithelial  tumours  of  the  mamma  ;  at  least,  I  know  of  no  well- 
authenticated  case,  that  can  be  cited  as  having  occurred  within  this 
period. 

Of  500  consecutive  cases  under  my  own  observation,  the  youngest 
was  twenty-four  years  of  age  at  the  onset  of  the  malady  ;  and  of  1,622 
similar  cases  tabulated  by  Gross,8  the  earliest  age  was  twenty-one  years. 
The  onset  of  mammary  cancer  before  twenty-five  is  a  great  rarity.  The 
earliest  duly  authenticated  cases  known  to  me,  are  Bryant's  9  at  20-5, 
and  Henry's 10  at  twenty-one  years. 

Alleged  examples  of  malignant  epithelial  mammary  tumours  by  Lyford 
at  eight  years,  Carmichael  at  twelve,  Cooper  at  thirteen,  Howe  at  fifteen 
etc.,  were  never  histologically  verified,  so  that  we  may  safely  assume  that 
in  these  cases  the  disease  was  really  sarcomatous,  of  which  examples 
have  been  reported  by  Chambert  at  four  months,  by  Vierregge  in  an 
infant,  and  by  Gross  at  nine  years.11 

Turning  now  to  the  other  extreme  of  life,  I  find  that  in  advanced  old    X 
age,  malignant  epithelial  tumours  seldom  originate.     The  published  cases 
of  this  kind  are  not  very  numerous. 

The  oldest  patient  known  to  me  is  the  woman  referred  to  by 
the  Registrar-General,  in  his  Report  for  1883,  who  died,  aged  106 
years,  with  "  cancer  of  the  eye  and  wrist,"  as  previously  men- 
tioned. 

1  Thomas'  "  Diseases  of  Women,"  1891,  p.  569. 

2  Kv.  din.  d.  Univ.  di  Napoli,  1890,  xi.,  p.  75. 

3  Cited  by  Gusserow,  Die  Neubildungen  des  Uterus,  1885,  S.  211. 

4  Arch.  f.  Oyn.,  1887,  Bd.  xxx.,  S.  471. 

5  Gaz.  hebd.  Med.  de  la  Russie  Meridional*,  1896,  No.  7. 

6  "  Surgical  Pathology,"  Hackley's  translation,  1879,  p.  694. 

7  Zeits.  f.  Heilkunde,  1888,  Bd.  ix.,  S.  337. 

8  International  Journal  of  the  Medical  Sciences,  March,  1888,  p.  220. 

9  Guy's  Hospital  Reports,  1891,  p.  337. 

10  Statist.  Mittheil.  uber  den  Brustkrebs  (I.  D.  Breslau,  1879). 

11  For  references  vide  my  book  on  "  Diseases  of  the  Breast." 


330  THE  NATURAL  HISTORY  OF  CANCER 

A  similar  case  is  that  of  a  lady,  under  the  care  of  Coker,1  who  died 
aged  106,  of  epithelioma  of  the  tongue. 

Briggs2  has  met  with  epithelioma  of  the  left  cheek  in  a  woman  103 
years  old  ;  and  Jalland,3  the  same  disease  of  the  lower  lip,  in  a  man 
102  years  old. 

Bryant 4  has  seen  a  malignant  epithelial  tumour  of  the  female  breast, 
which  was  first  noticed  at  the  phenomenal  age  of  ninety-six  ;  Lunn  5  has 
described  a  similar  tumour  of  the  mamma,  in  a  man  aged  ninety-one  ; 
and  Gurlt 6  cancer  of  the  stomach,  in  a  man  aged  ninety-two. 

An  instance  of  epithelioma  of  the  cervix  uteri,  in  a  woman  aged 
ninety-three  years,  has  been  reported  by  Findley ; 7  and  several  cases 
of  this  form  of  malignant  uterine  disease,  at  ninety  years  and  upwards, 
have  also  been  recorded. 

With  regard  to  malignant  epithelial  tumours  in  general,  it  may  be 
stated  that  under  the  age  of  puberty,  they  are  practically  unknown  : 
during  the  fourth  quinquenniad  a  few  cases  may  exceptionally  be  met 
with,  but  its  occurrence  before  twenty-five  is  a  great  rarity.  In  the  third 
decennium  more  cases  occur,  but  their  number  is  still  small.  Subse- 
quently the  numbers  rise  with  increasing  frequency  up  to  sixty-five, 
when  they  attain  their  maximum.  After  seventy-five  the  disease  is  much 
rarer  ;  and,  at  more  advanced  ages,  the  falhng-off  is  still  more  marked. 

To  sum  up  :  we  learn  from  the  foregoing  facts,  that  while  the  forces 
of  growth,  development  and  reproduction  are  in  greatest  activity — during 
the  periods  of  pre-natal  life,  infancy,  childhood,  adolescence,  and  adult 
age — the  tendency  to  malignant  tumours  of  any  kind  is  exceedingly 
small.  In  both  sexes,  the  disease  begins  to  be  frequent,  as  soon  as  the 
period  of  perfection  has  been  attained,  i.e.,  after  the  thirty-fifth  year  ; 
during  middle  age  and  the  decline  of  life  the  proclivity  to  it  increases, 
until  about  the  sixty-fifth  year  ;  after  which  it  becomes  relatively  less 
frequent,  and  increasingly  so  as  age  advances. 

The  principles  that  govern  the  age  incidence  of  malignant  disease  in 
general,  apply  also  to  its  various  local  manifestations  in  both  sexes. 
That  some  parts  of  the  body — such  as  the  uterus,  ovary  and  mamma — 
are  attacked  earlier  than  others,  may  be  ascribed  to  the  fact  that  the 
former  attain  maturity  earlier  than  the  latter. 

The  general  rule  for  the  uterus,  ovary,  breast  and  all  organs  is,  that 
their  liability  to  malignant  disease  begins  with  the  decline  of  their  func- 
tional activity,  and  increases  while  this  is  progressing. 

Thus  the  liability  to  malignant  disease  waxes,  as  the  developmental 
and  reproductive  activities  wane.  The  antagonism  between  the  forces 
of  growth,  development  and  expenditure  is  the  same  in  pathology,  as  in 
physiology.  It  is  owing  to  the  varied  interactions  of  forces  thus  called 
into  existence,  that  the  constitution  is  so  different  at  different  periods  of 
life  ;  and  that  each  period  has  its  special  morbid  proclivities. 

1  British  Medical  Journal,  March  5,  1887  :   "  Additional  Report  on  Centenarians." 

2  St.  Louis  Medical  and  Surgical  Journal,  U.S.,  1887,  vol.  liii.,  p.  150. 

3  British  Medical  Journal,  May  9.  1891.          4  "  Diseases  of  the  Breast,"  1887,  p.  149. 
6  Transactions  of  the  Pathological  Society,  London,  1897,  vol.  xlviii.,  p.  247. 

6  Arch.  f.  klin.  Chir.,  1880,  Bd.  xxv.,  S.  420. 

7  American  Journal  of  Obstetrics,  etc..  February,  1902,  p.  524. 


THE  INFLUENCE  OP  AGE  331 

Type,  variation  and  correlation,  all  change  with  the  age  of  the  indi- 
vidual. At  present  we  know  hardly  anything,  as  to  the  nature  of  the 
metabolic  reactions  underlying  these  changes  ;  but  it  is  to  the  physio- 
logical chemist  that  we  must  look,  for  clearing  up  this  difficult  problem. 

In  a  general  way,  it  may  be  said  that  integrative  changes  predominate 
during  the  earlier  part  of  the  developmental  cycle,  when  growth  is  most 
active  ;  alternate  excesses  of  integrative  and  disintegrative  activities, 
characterize  its  middle  part ;  and,  as  the  cycle  nears  its  terminus,  the 
latter  manifestations  tend  to  predominate.  It  is  as  the  outcome  of  dis- 
turbances in  the  rhythm  of  growth,  during  these  post-meridian  stages, 
that  malignant  and  other  tumours  are  most  prone  to  arise.  Thus  these 
belong  to  the  disintegrative  order  of  activities. 

In  this  we  have  an  illustration  of  the  universal  biological  law,  that 
growth  varies  according  to  the  surplus  of  nutrition  over  expenditure. 
So  long  as  the  surplus  exists — that  is  to  say,  while  nutrition  is  relatively 
high — simple  continuous  growth  is  maintained  ;  but,  when  nutrition  is 
relatively  low — that  is  to  say,  when  it  is  nearly  equalled  by  expenditure 
— new  centres  of  development  are  apt  to  arise,  and  growth  tends  to 
become  discontinuous. 

Changes  of  nutrition  determine  the  transition  from  the  one  to  the/ 
other  mode  of  growth.     To  the  operation  of  such  causes,  as  I  have  else- 
where maintained,1  the  origin  of  malignant  and  other  neoplasms  must 
ultimately  be  ascribed. 

1  "The  Principles  of  Cancer  and  Tumour  Formation,"  1888;  also  Chapters  VII.  and 
IX.  of  the  present  work. 


CHAPTER  XVI 

^TIOLOGICAL  INDICATIONS  DERIVED  FROM  THE  STUDY  OF  THE 
LIFE-HISTORY  OF  CANCER  PATIENTS 

Nutrition  and  Cancer. 

IN  preceding  chapters x  I  have  instanced  many  facts,  which  indicate 
that  the  causation  of  cancer  is  intimately  connected  with  nutrition  and 
the  conditions  of  existence  ;  and  it  is  especially  such  influences  as  are 
comprised  under  the  terms  alimentation  and  domestication,  that  seem 
to  me  to  be  of  paramount  importance. 

I  have  now  to  refer  to  some  other  items  of  information,  bearing  on 
this  subject. 

Long-continued  observation  of  cancer  patients,  in  the  early  stage  of 
the  disease,  has  convinced  me,  that  most  of  those  affected  are  large, 
robust,  well-nourished,  florid  persons,  who  appear  to  be  overflowing  with 
health  and  vitality.  Such  persons  have  large  appetites,  good  digestions, 
and  exceptionally  large  assimilative  power  ;  hence  they  often  present  a 
considerable  amount  of  embonpoint.  Mr.  and  Mrs.  John  Bull,  as  so 
frequently  depicted  in  the  pages  of  Punch,  are  the  physical  types  of  the 
majority  of  cancer  patients.  Such  types  are  indicative  of  general  hyper- 
nutrition. 

Careful  study  of  the  life-history  of  centenarians  and  of  persons  of 
advanced  age — who,  as  we  have  seen,2  are  very  rarely  the  victims  of 
cancer — shows  that  they  are  generally  of  spare  figure,  medium  height, 
and  that  they  eat  frugally,  taking  but  little  meat  and  alcohol.  The 
bulky,  overfed  type  of  being,  seldom  attains  to  great  age.  This  is 
probably  the  explanation  of  the  rarity  of  cancer  in  the  aged,  to  which  I 
have  previously  referred  ;  and  in  like  manner  it  is  alleged  that  the 
monks  and  nuns,  who  lead  abstemious  lives  and  eat  little  or  no  flesh 
food,  rarely  succumb  to  this  disease. 

The  Cancer  Type. 

Beneke3  has  described  those  predisposed  to  cancer  as  having  large 
hearts  and  wide  arteries,  with  small  lungs  and  pulmonary  artery  ;  4  long, 
large  and  capacious  intestines,  with  well-developed  osseous  and  muscular 
systems,  and  abundant  adipose  tissue.  This  quite  accords  with  what  I 

1  Chapters  II.,  III.,  IX.,  and  XV.  -  Chapter  XV. 

3  "  Constitution  und  constitutionelles  Kranksein  des  Menschen,"  Marburg,  1887. 

4  Here  it  may  be  mentioned  that  in  the  tuberculous— as  indicated  by  Fothergill  and 
others — just  the  converse  obtains — viz.,  small  heart  and  large  lungs — thus  adding  one 
more  to  the  list  of  contrasts  furnished  by  the  subjects  of  these  two  maladies. 

332 


^TIOLOGICAL  INDICATIONS  333 

have  myself  observed,  that  cancer  patients  usually  are  of  a  coarse  physical 
type.  Those  recently  attacked  never  present  a  cachectic  appearance. 
The  small,  pale,  ill-nourished  women,  of  the  type  so  familiar  in  Lanca- 
shire and  other  large  industrial  centres,  where  women-workers  abound, 
are  seldom  the  victims  of  this  disease. 

It  has  lately  been  argued  by  Cattin,1  that  there  is  some  connexion 
between  hypoplasia  and  cancer  ;  but,  with  the  exception  of  the  smallness 
of  the  lungs  and  pulmonary  artery,  to  which  I  have  just  referred,  I 
have  never  met  with  anything  that  could  be  adduced  in  favour  of  such 
a  suggestion.  No  doubt  persons  with  imperfectly  developed  and  pre- 
maturely exhausted  sexual  organs  are  unduly  prone  to  cancer,  as  I  have 
had  occasion  to  indicate  in  a  previous  chapter,2  and  it  is  in  this  category 
that  most  of  the  cases  cited  by  Cattin  should  be  included  ;  but,  these 
cases  form  a  special  group,  and  it  is  unquestionably  true  that  the  majority 
of  cancer  patients  have  a  well-developed  sexual  system,  as  is  proved  by 
the  large  proportion  of  them  who  marry  and  are  prolific. 

Obesity. 

It  was  a  prevalent  belief  in  former  times,  that  the  obese  were  unduly 
prone  to  cancer,  and  it  ought  not  to  be  difficult  for  those  who  have  oppor- 
tunities of  studying  the  life-history  of  the  obese,  to  thoroughly  test  this 
matter  ;  but  I  am  not  at  present  aware  of  any  satisfactory  data  bearing 
on  the  subject. 

The  connexity  between  obesity  and  cancer,  was  long  ago  remarked  on 
by  J.  H.  Bennet,3  who  says  :  "  If  a  tendency  to  fat  be  an  antidote  to 
tubercle,  as  I  believe  it  is,  spareness  may  possibly  be  considered  opposed 
to  cancer.  In  the  one  case,  we  should  do  all  we  can  to  bring  the  nutri- 
tion up  to  and  above  the  average  :  in  the  other,  down  to  or  below  it." 
Elsewhere  he  adds  :  "  The  circumstances  which  diminish  obesity  and  the 
tendency  to  the  formation  of  fat,  seem  to  be  opposed  to  the  cancerous 
tendency."  I  believe  there  is  a  sufficient  amount  of  truth  in  these 
suggestions,  to  justify  me  in  reproducing  them  here  ;  at  any  rate,  the 
obese  are  high  feeders  and  great  meat-eaters,  and  they  are  seldom  the 
victims  of  tubercle. 

I  have  seen  a  statement  by  R.  Bell,4  to  the  effect  that  the  thyroid  is 
invariably  more  or  less  atrophied  in  cancer  patients  ;  but  what  validity 
attaches  to  it,  I  am  unable  to  say.  The  suggestion  should,  however, 
receive  the  attention  of  pathologists,  with  the  view  of  confirming  or  con- 
futing it,  especially  as  some  obesity  is  often  a  characteristic  of  the 
cancerous. 

Blood-Pressure. 

Lately  considerable  attention  has  been  given  to  the  rise  of  the  blood- 
pressure  in  later  life — which  is  generally  associated  with,  and  perhaps 
caused  by,  sedentary  habits,  excess  of  food,  and  perverted  metabolism — • 

1  Jowin.  de  Med.  et  de  Chir.  pratiques,  April  10,  1905.  2  Chapter  IX. 

3  "  Cancerous  and  Cancroid  Growths,"  Edinburgh,  1849,  p.  251. 
*  New  York  Medical  Record,  February  16,  1907,  p.  260. 


334  THE  NATURAL  HISTORY  OF  CANCER 

and  some  authors  have  maintained  that  conditions  of  this  kind  give 
proclivity  to  cancer.  There  has  certainly  been  great  increase  in  the 
mortality  from  diseases  of  the  circulatory  system,  during  the  last  half- 
century,  especially  at  age-periods  above  the  thirty-fifth  year,  and  it  is 
probable  that  the  conditions  responsible  for  this  increase,  are  similar  to 
those  which  predispose  to  cancer  ;  but,  it  has  not  yet  been  proved,  that 
the  cancerous  are  more  prone  to  increased  blood-pressure  than  the  non- 
cancerous. 

According  to  my  investigations,  however,  cancer  patients  are  unduly 
prone  to  heart  disease  ;  and  I  have  also  found  that  the  relatives  of  cancer 
patients  have  special  proclivity  to  apoplexy,  heart  disease,  rheumatic 
fever  and  other  arthritic  manifestations. 

It  has  been  suggested,  that  the  abandonment  of  venaesection  has 
played  a  part  in  the  increase  of  this  type  of  disease  and  of  cancer,  and 
it  well  may  be  so  ;  but  nothing  of  the  nature  of  proof  has  been  adduced 
in  this  connexion. 

Diabetes. 

It  is  well  known  that  malignant  tumours  are  rich  in  glycogen  ;  and 
that  the  blood  of  those  who  bear  these  tumours,  contains  an  excess  of 
sugar-forming  substances.1  Of  late,  many  instances  have  been  reported 
of  the  concurrence  of  malignant  tumours  and  diabetes  (Boas,  Kappeler, 
Kreutzmann,  Tuffier  etc.)  ;  and,  it  has  been  suggested,  that  the  diabetic 
state  favours  their  development.  On  the  other  hand,  the  diabetic  state 
was  very  seldom  noticed  in  the  numerous  cancer  patients  under  my  own 
observation ;  and  other  pathologists  have  also  remarked  on  the  rarity  of 
this  conjunction.  Even  when  the  pancreas  is  the  seat  of  malignant 
disease,  diabetes  is  far  from  common. 

Boas,2  however,  reports  that  of  366  patients  with  intestinal  cancer 
tabulated  by  him,  12  were  also  affected  with  diabetes. 

Of  62  examples  of  this  concurrence,  collected  by  Kappeler,3  the  seats 
of  the  cancerous  disease  were  as  follows  : — breast  in  18,  mouth  12,  stomach 
or  liver  12,  uterus  3,  rectum  2,  colon  and  ovary  each  in  1  case  etc. 

Frerichs,  having  noted  the  cause  of  death  of  200  diabetic  patients, 
found  that  6  had  died  cancerous,  which  is  a  very  small  proportion. 

During  the  last  half-century,  the  mortality  from  diabetes  has  greatly 
increased  in  our  country,  and  so  also  has  the  amount  of  sugar  consumed 
as  food. 

Finally,  it  may  be  mentioned  that  diabetes  is  a  disease  to  which  the 
Jewish  race  is  specially  prone  ;  but,  as  we  have  already  seen,  their  pro- 
clivity to  cancer  is  rather  less  than  that  of  non- Jews.4 

Thus,  there  is  lack  of  conclusive  evidence  as  to  any  definite  setiological 
relationship  between  the  diabetic  state  and  cancer  ;  but,  diabetics  are 
known  to  be  unduly  prone  to  tubercle. 

1  According  to  Gulland,  the  blood  of  cancer  patients,  in  the  early  stage  of  the  disease, 
is  free  from  glycogen  ;  although,  when  the  malady  is  advanced,  this  substance  abounds 
in  it  (British  Medical  Journal,  1904,  vol.  i.,  p.  880). 

2  Berlin,  klin,  Woch.,  March  16,  1903. 

3  These  de  Paris,  1898.  *  Chapter  II. 


^TIOLOGICAL  INDICATIONS  335 


Arthritism. 

I  believe  it  is  owing  to  the  researches  of  Verneuil,  Isch-Wall  and 
others  of  this  school,  during  the  latter  part  of  the  nineteenth  century, 
that  some  connexion  was  first  shown  to  exist  between  arthritism  and 
cancer.  My  researches  certainly  show,  that  the  members  of  cancer  . 
families  are  unduly  prone  to  arthritic  manifestations  —  especially  to  X 
rheumatic  fever  and  heart  disease  ;  thus,  of  267  female  cancer  patients 
under  my  observation,  24  had  previously  suffered  from  rheumatic  fever, 
and  nearly  as  many  from  other  rheumatic  affections  :  and  of  160  similar 
cases  analysed  by  Nunn,  arthritic  affections  were  traced  in  15.  There 
is  also  evidence  of  a  considerable  amount  of  .rheumatic  fever  and  heart 
disease,  among  the  brothers  and  sisters  of  the  cancer  patients  in  my 
list ;  moreover,  of  154  parents  of  these  patients,  12  had  died  of  heart 
disease,  or  1  in  12-8,  whereas  in  the  general  community,  at  that  time,  the 
corresponding  ratio  was  1  in  79  ;  from  rheumatic  fever  my  analysis  shows 
1  death  in  154  parents,  the  corresponding  ratio  for  the  community  at 
large  being  1  in  195. 

Here  it  may  be  mentioned,  as  I  shall  subsequently  have  occasion  to 
prove,  that  gall-stones  are  of  more  frequent  occurrence  in  the  cancerous    ^ 
than  in  the  non-cancerous. 

The  Bonaparte  family  furnishes  a  concrete  example  of  the  connexity 
of  these  morbid  conditions,  Pierre  having  died  from  heart  disease  conse- 
quent on  rheumatic  fever,  and  Napoleon  III.  from  stone  in  the  bladder  : 
two  other  members  of  the  family,  Jerome  and  his  son  Napoleon,  suffered 
from  diabetes  ;  while  Napoleon  I.,  his  father,  his  brother  Lucien,  and  bis 
sisters  Caroline  and  Pauline,  all  died  from  cancer  of  the  stomach. 

According  to  Charcot,  "  Heberden's  nodes  " — which  he  regards  as 
pathognomonic  of  the  rheumatic  diathesis — are  not  uncommonly  met 
with  in  the  subjects  of  mammary,  uterine  and  some  other  local  forms 
of  cancer  ;  and  we  know  that  severe  forms  of  heart  disease  are  com- 
paratively frequent,  in  those  who  bear  these  stigmata. 

It  has  been  suggested  by  Haig,  that  the  special  factor  in  arthritism 
which  gives  proclivity  to  cancer,  is  an  excess  of  uric  acid  in  the  tissues  ; 
but  not  the  slightest  evidence  has  been  adduced  in  support  of  this  con- 
tention. 

Finally,  there  are  good  reasons  for  believing  the  arthritic  predis- 
position to  be  in  some  way  antagonistic  to  tubercle,  as  is  specially 
obvious  in  the  case  of  the  gouty. 

Osteitis  Deformans. 

Some  years  ago,  Paget 1  published  an  account  of  :  "A  form  of  chronic 
inflammation  of  bones  (osteitis  deformans),"  which  was  often  complicated 
by  malignant  tumour  ;  this  was  the  condition  in  three  of  his  five  cases. 
Other  examples  of  this  concomitancy  were  subsequently  reported  by 
Cayley,  Goodhart,  Howse,  Lunn  etc.,  so  that  the  impression  arose  that 
this  form  of  bone  disease  was  often  complicated  by  cancer. 

1  Transactions  of  the  Medico-Chirurgical  Society,  London,  1877,  vol.  lx.,  p.  37. 


336  THE  NATURAL  HISTORY  OF  CANCER 

With  regard  to  this,  I  have  to  point  out  that  of  over  1,000  cases  of 

malignant  disease  investigated  by  me,  and  of  which  I  now  have  the 

y  records,  not  a  single  one  was  complicated  by  osteitis  deformans  :  in  this 

list  170  cases  of  breast  cancer  in  women,  and  160  cases  of  uterine  cancer 

are  comprised. 

In  most  of  Paget's  cases,  as  well  as  in  those  subsequently  reported, 
the  malignant  tumours  affected  the  skeletal  bones  ;  and,  it  seems  prob- 
able, that  this  malady  should  be  classed  with  the  recently  discriminated 
"  multiple  myeloma,"  whether  associated  with  albumosuria  or  not. 


Gall-stones.1^ 

£In  this  place'reference  must  also  be  made  to  the  incidence  of  gall- 
stones, which  certainly  are  of  more  frequent  occurrence  in  the  cancerous 
than  in  the  non-cancerous. 

According  to  Brockbank,  in  England,  gall-stones  are  met  with  in 
4-4  per  cent,  of  the  hospital  inmates — males  2-9  and  females  7-9  per  cent. 
Among  the  whites  of  the  United  States,  Mosher  found  that  the  records 
of  1,037  necropsies  yielded  7-85  per  cent,  of  gall-stones — males  5-49  and 
females  9-37  per  cent.  In  this  country,  according  to  Rolleston,  gall- 
stones are  present  in  8-5  per  cent,  of  all  necropsies  on  adults  ;  and, 
according  to  Kehr,  in  10  per  cent.1 

On  the  other  hand,  in  the  cancerous,  Muir  found  gall-stones  in  13  out 
of  103  necropsies,  or  in  12-6  per  cent.  ;  of  67  men  in  7-9  per  cent.,  and 
of  40  women  in  20  per  cent. 

Of  281  cancer  necropsies  analysed  by  me  (in  which  no  hepatic  or 
gastric  cancers  are  included),  gall-stones  were  noted  in  18,  or  in  6-4  per 
cent.  :  100  were  men,  with  gall-stones  in  4  cases  ;  and  181  women,  with 
gall-stones  in  14,  or  7-7  per  cent. 

It  is  generally  believed  that  gall-stones  are  more  frequently  found  in 
association  with  cancer  of  the  stomach  and  liver,  than  with  any  other  of 
the  local  manifestations  of  the  disease  ;  and,  it  accords  with  this,  that 
in  a  series  of  cancer  necropsies  comprising  a  due  proportion  of  these 
localizations,  Colwell  found  gall-stones  two  and  a  half  times  as  frequent 
in  the  cancerous  as  in  the  non-cancerous. 

T  Thus  the  cancerous,  like  the  tuberculous  and  the  insane,  are  more 
prone  to  gall-stones  than  the  generality  of  the  population  of  corresponding 
age  and  sex. 

As  further  evidence  of  the  perverted  metabolism  commonly  associated 
with  the  predisposition  to  gall-stones,  it  may  be  mentioned  that  of  115 
necropsies  on  the  bodies  of  persons  thus  affected,  Mosher  found  marked 
arterio-sclerosis  in  50. 

According  to  Murchison,  the  tendency  to  gall-stones  is  fairly  often 
associated  with  proclivity  to  urinary  gravel. 

Gall-stones  are  believed  to  be  of  more  frequent  occurrence  among  the 
rich,  than  the  poor  ;  while  the  obese  and  those  of  sedentary  habits,  are 
said  to  be  specially  liable. 

1    Vide  also  Chapter  XI. 


^TIOLOGICAL  INDICATIONS  337 

Tubercle  and  Cancer. 

In  some  of  the  earlier  chapters  of  this  work,1  I  adduced  a  mass  of 
detailed  information,  as  evidence  of  the  fact  that,  in  temperate  climates, 
the  incidence  of  tubercle  and  cancer  is  determined  by  the  local  conditions 
of  existence,  in  such  wise  that  tuberculous  diseases  are  rarest  where 
cancer  is  most  prevalent  and  vice  versa.  In  tropical  countries  malaria 
may  be  regarded  as  taking  the  place  of  tubercle. 

Another  fact  elicited  was,  that  the  great  increase  of  cancer  during 
the  last  half-century,  has  coincided  with  remarkable  decline  in  the 
mortality  from  tuberculous  diseases — especially  phthisis  ;  and  it  was 
shown  that  this  connexity  also  was  due  to  variation  in  the  local  con- 
ditions of  existence,  with  respect  to  which  these  two  maladies  are  inversely 
related. 

When  treating  of  the  family  history  of  cancer  patients  in  a  subse- 
quent chapter,  I  shall  adduce  evidence  to  show  that  a  large  proportion 
of  cancerous  persons  are  the  surviving  members  of  tuberculous  families  ; 
and.  it  is  this  heritable  condition,  that  gives  such  persons  their  special 
proclivity  to  malignant  disease,  when  exposed  to  certain  conditions  of 
existence.  In  short,  I  think  there  can  be  no  doubt,  that  those  who 
survive  the  peculiar  kind  of  degeneracy  associated  with  the  tuberculous 
predisposition,  are  at  a  later  period  of  life  specially  prone  to  cancer. 

At  first  sight,  there  may  seem  to  be  some  difficulty  in  reconciling  this 
conclusion,  with  the  appearance  of  rude  health  which,  as  I  have  shown, 
characterizes  most  of  those  predisposed  to  cancer  ;  but  in  reality  there 
is  here  no  contradiction,  for  it  commonly  happens  that  the  surviving 
members  of  tuberculous  families,  although  they  never  develop  cancer, 
are  remarkable  for  their  robust  appearance  and  longevity.  The  famous 
Astley  Cooper  was  a  striking  example  of  this,  yet  he  was  of  a  very 
tuberculous  family,  having  lost  five  near  relatives  from  this  disease ;  more- 
over, in  his  youth,  he  had  haemoptysis,  which  was  rightly  supposed  to 
be  due  to  pulmonary  tubercle,  for  when — in  accordance  with  his  last 
instructions — his  body  was  submitted  to  post-mortem  examination,  a 
healed  tuberculous  lesion  was  found  at  the  apex  of  his  lung. 

The  much  greater  frequency  with  which  obsolescent  tuberculous 
lesions  are  found  in  association  with  cancer,  than  with  most  other  diseases, 
also  tells  in  favour  of  this  view. 

Thus,  of  136  consecutive  necropsies  on  women  under  my  observation 
who  died  of  cancer  (uterus  79,  breast  44,  rectum  13),  obsolete  pulmonary 
tubercle  was  found  in  17,  or  in  12-5  per  cent.  ;  whereas,  of  16,562  consecu- 
tive necropsies  tabulated  by  Heitler,2  on  the  bodies  of  those  who  had 
died  in  the  Vienna  Pathological  Institute  of  various  causes,  which  included 
but  1 10  cases  of  cancer,  obsolete  tubercle  was  met  with  only  in  789  cases, 
or  in  4-7  per  cent. 

In  collecting  these  data,  it  is  important  to  note  that  only  well-marked, 
macroscopical,  gross  lesions,  were  taken  into  account ;  for,  when  modern 
microscopical  methods  of  research  are  fully  utilized,  tuberculous  lesions 

1  Chapters  II.,  III.,  IV.,  and  IX.  2   Wiener  Klinik.,  1879,  S.  269. 

22 


338  THE  NATURAL  HISTORY  OF  CANCER 

can  be  demonstrated  in  almost  every  corpse,  as  the  researches  of  Naegeli,1 
Brouardel  and  others  have  proved. 

£      The  outbreak  of  cancer  often  follows,  or  coincides  with,  the  healing 
of  tubercle. 

Although  these  two  diseases  are  thus  shown  to  be  intimately  corre- 
lated, it  is  nevertheless  very  rare — considering  the  great  frequency  of 
both to  find  cancer  and  tubercle  in  active  progress  in  the  same  indi- 
vidual. I  have  met  with  this  conjunction  only  twice  in  136  cancer 
necropsies ;  and  Kelynack,2  at  the  Manchester  Infirmary,  found  it  only 
twice  in  145  similar  necropsies.  Other  analyses  of  this  kind  by  various 
authors  (Zahn,  Moak,  MacCasky,  Boas  etc.)  give  similar  results.  Hence, 
there  is  obviously  decided  antagonism,  between  active  tuberculous  and 
cancerous  manifestations. 

I  am  inclined  to  believe,  as  F.  P.  Weber  has  suggested,  that  in  most 
cases  of  this  concomitancy,  the  active  tuberculous  disease  is  due  to  the 
rekindling  of  old  quiescent  foci,  by  the  lowering  of  the  patient's  general 
vitality,  consequent  on  the  progress  of  the  cancerous  disease. 

It  is  evident  from  the  foregoing  indications,  that  active  tuberculous 
disease  is  of  very  much  less  frequent  occurrence  in  the  cancerous,  than 
in  the  non-cancerous. 

With  regard  to  tubercle  in  general — active  as  well  as  obsolete — there 
can  be  no  doubt  that  the  cancerous  are  less  prone  to  it  than  the  non- 
cancerous  :  thus,  of  569  cancerous  persons,  Lubarsch  3  found  that  20-6  per 
cent.4  presented  tuberculous  lesions  ;  whereas,  of  5,967  non-cancerous 
persons,  42-7  per  cent,  were  tuberculous  ;  similarly  of  65  cancerous 
persons,  forty  years  old  and  upwards,  Nicholls  5  found  that  9  per  cent, 
were  tuberculous  ;  whereas,  of  279  non-cancerous  persons  of  similar  ages, 
19  per  cent,  were  tuberculous. 

The  available  statistical  data  also  indicate,  that  cancer  is  of  much 
less  frequent  occurrence  in  the  tuberculous,  than  in  the  non-tuberculous  : 
thus  of  Lubarsch's  2,668  tuberculous  cases,  4-4  per  cent,  were  cancerous  ; 
whereas,  of  his  3,868  non-tuberculous  cases,  11-7  per  cent,  were  can- 
cerous :  similarly  of  Nicholls's  60  tuberculous  persons,  forty  years  old 
and  upwards,  10  per  cent,  were  cancerous  ;  whereas,  of  his  243  non- 
tuberculous  persons  having  the  same  age  distribution,  22-2  per  cent,  were 
cancerous. 

Considering  the  great  frequency  of  both  maladies,  the  comparative 
rarity  of  their  coexistence  is  remarkable  ;  and  a  certain  antagonism  is 
thus  indicated,  which,  however,  falls  far  short  of  absolute  incompati- 
bility. 

A  somewhat  similar  inverse  relationship  of  tubercle  and  cancer  is 
also  noticeable  in  respect  to  site  incidence  ;  for  tubercle  very  rarely 
originates  in  the  localities  where  cancer  commonly  arises,  and  vice 
versa.  Thus  the  stomach,  liver,  uterus  and  mamma,  the  commonest 
seats  of  origin  of  cancer,  are  comparatively  seldom  the  seats  of  primary 

1  Arch  f  path.  Amt.,  1900,  Bd.  clx.,  S.  426.  2  Medical  Chronicle,  June,  1897. 

3  Arch.  f.  path.  Anat.,  1888,  Bd.  cxi.,  S.  305. 

,|V!t3  ftiS?  PfrceTntage  than  most  pathologists  have  found,  e.g.,  Kelynack  14"4, 
my^lf  14,  G.  Forbes  12'5,  Le  Goupils  8'3,  Cohen  5,  etc. 
6  Montreal  Medical  Journal,  1903,  vol.  xxxii.,  p.  333. 


^TTIOLOGICAL  INDICATIONS  339 

tuberculous  disease  ;  and  even  secondary  tuberculous  manifestations,  are 
uncommon  in  these  localities  :  in  short,  over  80  per  cent,  of  all  malignant 
tumours,  arise  in  localities  where  tubercle  is  seldom  met  with. 

On  the  other  hand,  the  lung — whence  such  an  immense  number  of 
cases  of  primary  tubercle  arise — very  seldom  originates  any  form  of 
malignant  disease  ;  thus,  only  17  cases  of  this  kind  are  included  in 
13,824  primary  malignant  tumours  of  my  list.  This  consideration  alone, 
suffices  to  negative  K.  Wolf's  contention,  that  local  tuberculous  lesions 
of  the  lungs  etc.  create  a  predisposing  cause  to  cancer. 

Moak l  has  attempted  to  account  for  this  antithesis,  by  calling  atten- 
tion to  the  different  age  incidence  of  the  two  maladies,  maintaining 
that  most  cases  of  pulmonary  tubercle  are  fatal  before  fifty  ;  and  most 
cases  of  cancer  after.  To  such  a  statement  as  this  it  may  be  objected — 
even  if  the  facts  were  correct — that  it  would,  nevertheless,  not  explain 
the  antithesis.  In  so  far,  however,  as  the  particular  local  forms  of  cancer 
above  referred  to  are  concerned,  the  correctness  of  the  statement  is  cer- 
tainly inadmissible  ;  for,  the  average  age  at  death  of  cancer  of  the  uterus, 
is  forty-four  years,  of  the  mamma  forty-eight,  and  of  the  stomach  47-4 
for  females,  and  fifty-one  for  males  ;  while,  as  to  the  mortality  from 
tubercle  of  the  lung,  the  national  statistics  show  that  this  attains  its 
maximum  in  the  decennium  thirty-five  to  forty-five.2 

In  this  form  of  antithesis,  as  in  the  others  I  have  had  occasion  to 
mention,  the  mutual  antagonism  falls  far  short  of  absolute  incompati- 
bility. Thus,  instances  of  the  coexistence  of  tubercle  and  cancer  of  the 
same  locality  etc.,  have  been  reported,  e.g.,  in  the  stomach  (Claude)  ;  in 
the  uterus  (Wallert  and  Franque)  ;  in  the  mamma  (Moak,  Kallenberger, 
Crawford  and  Warthin)  ;  in  the  liver  (Frerichs)  ;  in  the  large  intestine 
(Dalton,  Zenker,  Naegeli,  and  Moak)  ;  in  the  rectum  (Naegeli  and  Baum- 
garten)  ;  in  the  small  intestine  (Lubarsch  and  Naegeli)  ;  in  the  larynx 
(Baumgarten,  Zenker  and  Crone)  ;  in  the  lung  (Batty  Shaw,  Schwalbe, 
Wolf,  Wilson  Fox  and  Friedlander)  ;  in  the  oesophagus  (Cordua) ;  in 
the  eye-sarcoma  (Silex)  etc.  Moreover,  many  instances  of  "  lupous 
cancer  "  have  also  been  described. 

It  will  be  gathered  from  the  foregoing,  that  while  the  outbreak  of 
cancer  not  unfrequently  follows  or  coincides  with  the  healing  of  tubercle, 
active  tuberculous  disease  is  very  rare  in  the  cancerous.  Thus,  while 
the  predisposition  to  tubercle  gives  proclivity  to  cancer,  there  is,  never- 
theless, a  certain  antagonism  between  active  tuberculous  and  cancerous 
manifestations,  the  special  causative  factors  which  favour  the  one  being 
inimical  to  the  other,  and  vice  versa. 

I  have  dwelt  at  some  length  on  the  inter-relations  of  these  maladies, 
because  they  appear  to  me  to  have  an  important  bearing  on  the  aetiology 
and  prophylaxis  of  cancer  ;  and,  so  far  as  I  know,  the  matter  has  never 
before  been  set  forth  in  its  true  light. 

1  Journal  of  Medical  Research,  1902,  vol.  viii.,  p.  128. 

2  An  analysis  of  161,920  cancer  deaths,  by  Dr.  J.  F.  Payne,  shows  that  83  per  cent, 
of  them  took  place  before  the  age  of  forty-five  ;  while,  of  361,000  phthisis  deaths,  only 
24  per  cent,  took  place  after  forty-five  ("  Cancer  in  Relation  to  Life  Assurance,"  1898). 

22—2 


340  THE  NATURAL  HISTORY  OF  CANCER 

Pleural  Adhesions,  Emphysema,  Cardiac  Changes  etc. 

Post-mortem  records  show  the  great  frequency  of  old  adhesions  of 
Vthe  pleurae  in  the  cancerous  :  thus,  of  my  79  necropsies  for  uterine  cancer, 
old  pleural  adhesions  were  present  in  no  less  than  41  cases  (general,  22 — 
of  which  20  were  bilateral ;  and,  in  16  cases,  these  adhesions  were  con- 
fined to  the  region  of  the  apex— both  in  10,  left  4,  right  2)  ;  similarly,  of 
44  necropsies  for  mammary  cancer  in  women,  old  pleural  adhesions  were 
noted  in  24  cases  (general  in  16 — of  which  13  were  bilateral ;  and,  in  8 
cases,  these  adhesions  were  in  the  region  of  the  apex). 

Thus,  of  these  123  necropsies,  old  pleural  adhesions  were  noted  in  65, 
or  in  more  than  half  of  all  the  cases.  Probably  most  of  these  pleural 
lesions  were  tuberculous  in  origin. 

With  regard  to  emphysema,  of  the  79  uterine  cancer  necropsies,  this 
condition  was  noted  in  23  :  and  of  the  44  mammary  cancer  post-mortems 
in  12 ;  thus,  of  these  123  necropsies,  emphysema  was  present  in  35,  or 
1  in  every  3 J. 

As  previously  mentioned,  in  the  earliest  stage  of  the  disease,  cancer 
>'  patients  have  large  hearts  and  wide  arteries,  with  small  lungs.  The 
natural  tendency  is  for  the  heart  and  arteries  to  increase  in  size  from 
childhood  to  old  age,  as  was  long  ago  shown  by  Bigot  and  Clendenning  ; 1 
but,  in  those  who  have  died  from  cancer,  the  heart  is  generally  small  and 
undersized,  with  corresponding  diminution  of  the  aorta  and  of  the  chief 
arterial  trunks.  These  changes  seem  to  be  secondary  to  alterations  in 
the  blood,  which  take  place  during  the  course  of  the  disease  ;  for,  not 
only  are  its  morphological,  chemical  and  physical  properties  changed, 
but,  as  the  experiments  of  Louis  show,  its  total  quantity  is  notably 
diminished. 

To  the  combined  operation  of  these  factors,  the  diminished  cardiac 
dulness  so  often  noticeable  in  cancerous  patients,  to  which  Gordon  2  has 
lately  called  attention,  may  no  doubt  be  ascribed. 


Malaria. 

A  few  years  ago  Loffler,3  reviving  an  ancient  and  wellnigh  forgotten 
j.  belief ,  suggested  that  there  is  an  antagonism  between  malaria  and  cancer  ; 
>and  proposed  to  treat  the  cancerous  with  injections  of  malarial  blood. 

The  main  support  for  this  conception  is  derived  from  the  fact,  that 
malaria  attains  its  maximum  in  the  tropics,  where  cancer  is  rare  ; 
moreover,  proceeding  from  the  equator  towards  the  poles,  as  malaria 
diminishes,  cancer  becomes  commoner. 

As  I  have  already  intimated,  this  correlated  variability  is  probably  the 
outcome  of  changed  conditions  of  existence,  rather  than  of  any  specific 
antagonism  between  the  two  maladies  ;  and  thus  also  may  be  explained 
the  comparative  rarity  of  tubercle  in  tropical  countries. 

In  our  own  country,  cancer  is  common  enough  among  the  inhabitants 
1  Medical  Gazette,  vol.  xxii.,  p.  450. 

Transactions  of  the  Medico-Chirurgical  Society,  1904,  vol.  Ixxxviii.,  p.  327. 
3  Deutsche  med.  Woch.,  October  17,  1901. 


.ETIOLOGICAL  INDICATIONS  341 

of  the  malarious,  marshy  flats  of  the  Essex  coast  and  its  vicintiy  ;  and, 
in  malarious  parts  of  Europe,  similar  conditions  have  been  noticed. 
Moreover,  cancer  is  of  as  frequent  occurrence  in  malarious  Italy,  as  in 
Ireland  and  Prussia,  where  malaria  is  almost  unknown  ;  while  in  Holland, 
malaria  and  cancer  are  both  common. 

The  occurrence  of  cancer  has  often  been  noted  in  malarious  subjects. 

Thus,  there  can  be  no  question  of  any  marked  incompatibility  between 
the  two  diseases  ;  although  it  is  not  improbable  that  the  impaired  nutrition 
determined  by  chronic  malaria,  may  be  a  condition  unfavourable  to  the 
onset  of  cancer,  but  of  this  convincing  evidence  is  lacking. 


Syphilis  and  Cancer. 

In  most  modern  communities  syphilis  is  a  common  disease,  at  least 
as  common  as,  or  even  commoner  than,  tubercle.  Syphilis  also  has  this 
peculiarity,  that  it  generally  stamps  its  victims  with  what  Ricord  has  so 
well  designated  as  "the  signature  of  syphilis " — marks  by  which  the  expert 
can  recognize  its  trail. 

Well,  I  have  looked  for  these  marks,  very  carefully,  in  a  large  number 
of  female  cancer  patients  ;  and  I  have  very  seldom  been  able  to  find  any 
trace  of  them — signs  of  congenital  syphilis  being  entirely  absent. 

Thus,  of  165  consecutive  female  breast-cancer  patients,  not  a  single 
one  presented  undoubted  signs  of  having  had  syphilis  ;  and,  of  160 
uterine-cancer  patients,  only  one  presented  signs  of  having  had  syphilis. 

Other  indications  furnished  by  careful  study  of  the  life-history  of 
these  patients  clearly  show,  that  they  are  seldom  the  victims  of  syphilis  : 
thus,  they  marry  earlier,  have  more  children,  and  fewer  miscarriages, 
than  the  majority  of  women  of  the  same  rank  in  life.  The  ensemble  of 
the  life-history  of  these  cancer  patients  shows  that  they  had  almost  in- 
variably led  regular,  sober,  industrious  and  healthy  lives  ;  and  not  a 
single  one  of  them  had  ever  been  addicted  to  prostitution,  so  far  as  I 
could  ascertain. 

I  have  never  seen  the  slightest  indication  that  would  support 
Esmarch's  contention,1  as  to  sarcoma  being  a  late  manifestation  of 
syphilis  in  the  second  or  third  generation  ;  and  I  believe  it  has  no  founda- 
tion in  fact. 

There  can  be  no  doubt  that  prostitutes,  drunken  and  dissolute  persons, 
notwithstanding  their  great  proclivity  to  venereal  and  syphilitic  affec- 
tions, are  less  subject  to  cancer  than  the  majority  of  women  of  their  own 
rank  of  life. 

Of  like  import  is  the  fact  that  cancer  is  rarest  in  the  slums  of  our    " 
large  towns,  where  syphilis  is  commonest. 

From  the  foregoing  and  from  other  indications  of  this  kind,  it  may  be 
inferred  that  the  victims  of  constitutional  syphilis,  are  much  less  prone  to 
cancer  than  the  non-syphilitic. 

This  comparative  immunity  of  the  syphilitic,  is  probably  due  to  the  v 
depraved  nutrition  and  lowered  vitality,  caused  by  contamination  of  the 

1  Arch.  /.  klin.  Chir.,  Bd.  xxxii.,  Heft  1. 


342  THE  NATURAL  HISTORY  OF  CANCER 

system  with  the  syphilitic  virus.  Turenne  was  probably  aware  of  this, 
when  he  syphilized  his  recently  operated  cancer  patients,  with  the  object 
of  preventing  recurrence. 

Here  it  may  be  mentioned  that  cancerous  diseases  are  met  with  in  the 
animal  world,  where  syphilis  is  unknown  ;  so  that  syphilis  cannot  be 
regarded  as  the  cause  of  cancer,  as  some  have  alleged. 

In  connexion  with  this  subject,  reference  may  be  made  to  the  immunity 
•Vof  these  female  cancer  patients  from  chronic  ulcer  of  the  leg.  of  which  there 
was  not  a  single  example  among  these  325  women.  Considering  the  com- 
monness of  the  latter  affection  in  women  over  middle  age,  this  immunity 
of  these  cancer  patients  is  certainly  highly  remarkable. 

In  the  eighteenth  century,  it  was  customary  to  establish  "  issues  " 
on  each  of  the  four  limbs,  after  operations  for  the  removal  of  cancer, 
with  the  object  of  preventing  recurrence  "  by  opening  a  passage  for  the 
cancerous  virus  ";  and,  under  the  influence  of  similar  ideas,  the  operation 
wounds  were  prevented  from  closing  by  first  intention.  It  is  probable 
that  such  methods  do  exert  some  deterrent  influence  on  the  disease, 
acting  like  the  syphilitic  virus — but  less  powerfully — by  lowering  the 
general  vitality. 

I  have  seen  it  stated  that  in  Eastern  Asia,  syphilis  and  leprosy  are 
c  generally  regarded  as  antagonistic  maladies  ;  and,  in  Europe,  the  decline 
of  leprosy  has  been  concomitant  with  the  rise  of  syphilis. 

Before  quitting  this  subject,  it  must  be  mentioned  that  a  few  very 
exceptional  instances  have  been  recorded,  of  cancerous  disease  arising 
from  these  chronic  ulcers  ;  and  from  various  syphilitic  and  other  lesions. 

Erysipelatous  and  Suppurative  Affections. 

It  has  been  urged  by  Lambotte x  and  others,  that  erysipelatous  and 
suppurative  affections  are  of  comparatively  rare  occurrence  in  the  can- 
cerous ;  and  the  inference  has  been  drawn,  that  these  maladies — by 
vaccinal  action — protect  from  cancer. 

In  order  to  test  the  value  of  the  alleged  rarity  of  erysipelas  in  the 
cancerous— which  is  at  variance  with  the  impression  I  had  formed  after 
an  extensive  experience  of  cancer— I  have  examined  the  statistical  data 
of  some  of  the  large  London  hospitals,  with  the  following  results. 

Of  395  extirpations  of  the  breast  for  cancer,  40  were  subsequently 
attacked  by  erysipelas,  or  10  per  cent. ;  whereas,  of  173  recent  scalp 
wounds,  under  treatment  at  one  of  these  hospitals  during  the  same  period, 
only  8  were  attacked  by  erysipelas,  or  4-6  per  cent. 

It  would  thus  appear— as  my  own  experience  suggested— that  instead 

being  immune  from  erysipelas,  the  cancerous  are  more  than  twice'  as 
prone  to  it  as  the  non-cancerous. 

Lambotte  also  states  that  there  is  seldom  any  evidence  of  suppurative 
ttections,  m  the  pathological  antecedents  of  the  cancerous. 

As  1  was  at  some  pains,  several  years  ago,  to  determine  the  maladies 
which  the  cancerous  are  prone,  I  find  that  I  have  at  hand  the  requisite 

i  for  testing  the  validity  of  this  statement. 

1  La  Presse  Mid.  Belye,  1896,  No.  21,  p.  161  ;  and  No.  35,  p.  274. 


^ETIOLOGICAL  INDICATIONS  343 

Thus,  of  130  uterine-cancer  patients  under  my  observation,  9  had 
previously  suffered  from  small-pox,  5  from  phthisis,  2  from  erysipelas, 

2  from  abscess,  2  from  fistula-in-ano,  and  1  each  from  necrosis,  lupus  and 
furunculosis. 

Of  130  breast-cancer  patients,  5  had  previously  suffered  from  phthisis, 
4  from  small-pox,  4  from  ulceration  of  the  uterus,  3  from  erysipelas, 

3  from  old  abscesses  of  the  neck,  and  1  each  from  fistula-in-ano,  suppura- 
tive  tuberculous  disease  of  the  knee-joint,  otorrhoea  and  whitlow. 

Thus,  of  these  260  female  cancer  patients,  46,  or  18  per  cent.,  had  pre- 
viously suffered  from  some  form  of  suppurative  disease. 

To  compare  with  the  foregoing,  I  have  found  that  of  75  women  with 
non-cancerous  tumours,  12  had  suffered  from  previous  suppurative 
diseases,  or  16  per  cent.,  as  follows  :  phthisis  3,  abscess  4,  erysipelas  2, 
and  1  each  from  small-pox,  ulceration  of  uterus  and  hip-joint  disease. 

From  this  it  appears  that  Lambotte's  second  proposition  is  as  un- 
reliable a,s  his  first  ;  for,  as  these  data  show,  the  cancerous  are  just  as  prone 
to  suppurative  diseases  as  the  non-cancerous. 

I  have  seen  a  great  many  cancer  patients  attacked  by  erysipelatous 
and  suppurative  affections  ;  but  I  have  never  noticed  consequent  marked 
amelioration  of  the  disease,  much  less  anything  approaching  a  cure.  In 
many  such  cases,  these  superinduced  affections  led  to  a  rapidly  fatal 
issue. 

I  believe  that  most  of  the  alleged  cures  of  malignant  disease  by 
erysipelas  inoculations  etc.  are  attributable  to  diagnostic  errors  ;  at 
any  rate,  I  am  convinced,  that  tuberculous,  syphilitic,  and  various  other 
chronic  inflammatory  pseudo-plasms  are  often  mistaken  for  malignant 
disease  by  experienced  surgeons,  especially  in  the  uterus  and  breast ; 
and,  I  suspect  that  cases  of  actinomycosis  and  other  parasitic  infections, 
are  more  frequently  mistaken  for  malignant  disease  than  is  generally 
believed.  Consequently,  every  new  specific  for  cancer  has  no  difficulty 
in  producing  a  crop  of  "  cures  "  to  justify  itself  ;  although  I  am  con- 
vinced that  cancer  has  never  really  been  cured,  by  any  external  applica-  V 
tion  or  internal  medicament  whatever. 

As  for  those  exceptional  cases  of  malignant  disease,  in  which — after 
an  attack  of  erysipelas  or  after  inoculation  with  its  toxins  etc. — arrest  or 
diminution  has  been  observed,  evidently  such  conditions  are  not  due  to 
any  specific  or  vaccinal  action  of  the  remedy,  for  similar  effects  have   * 
been  produced  by  many  widely  different  conditions. 

For  instance,  many  examples  of  the  regression  of  mammary  cancer, 
in  connexion  with  acute  outbreaks  of  pulmonary  tubercle  have  been  ' 
reported.  Perrion  has  seen  the  same  disease  subside,  after  an  operation 
for  goitre,  followed  by  much  suppuration.  Teallier  has  noticed  retarda- 
tion in  the  progress  of  uterine  cancer  during  lactation.  An  instance  of 
the  regression  of  mammary  sarcoma,  after  artificially  induced  delivery, 
has  been  reported  by  Jahr.  In  cases  of  intra- abdominal  malignant  dis- 
ease, Bidwell  and  others  have  seen  marked  amelioration  ensue,  after  simple 
exploratory  laparotomy.  Beatson's  cases  of  regression  of  mammary 
cancer  after  oophorectomy  evidently  belong  to  this  category.  Similar 
results  have  ensued  after  injections  of  tuberculin,  the  toxins  of  erysipelas 


344  THE  NATURAL  HISTORY  OP  CANCER 

etc.  Many  other  such  instances  might  be  cited.  In  the  penultimate 
stages  of  the  cancerous  cachexia  and  most  exhaustive  illnesses,  malignant 
growths  often  become  stationary  ;  and  even  appear  to  wither  and  dry  up, 
shortly  before  death.  Blanchard  and  Fleury  have  reported  instances  of 
this  kind,  in  connexion  with  uterine  cancer  etc. 

The  only  feature  common  to  all  such  cases  is,  the  extremely  debilitated 
condition  to  which  the  patients  are  reduced  ;  and  I  think  there  can  be  no 
doubt,  that  enfeebled  vitality  is  the  cause  of  such  improvement  as  is 
noticeable.  The  condition  of  the  patient  is,  in  fact,  similar  to  that  brought 
about  by  the  starvation  treatment  of  cancer,  as  formerly  practised  with 
some  success  by  Hufeland  and  others. 


Infectious  Diseases. 

By  careful  study  of  the  life-history  of  cancer  patients,  I  have  found 
that  those  who  subsequently  develop  this  malady,  are  even  more  prone 
to  infectious  diseases  than  the  non-cancerous. 

Thus,  of  my  267  female  cancer  patients,  13  had  suffered  from  small- 
pox (4-8  per  cent.),  16  from  typhoid  fever  (6  per  cent.),  and  1-1  per  cent. 
from  pneumonia  ;  whereas,  of  83  women  with  non-cancerous  tumours, 
1-2  per  cent,  had  suffered  from  small-pox,  6  per  cent,  from  typhoid,  and 
2  per  cent,  from  pneumonia. 

According  to  Lubarsch,  those  actually  suffering  from  cancer  are  seldom 
attacked  by  infectious  diseases  ;  thus,  among  his  569  cancer  patients, 
not  a  single  instance  of  diphtheria,  typhoid  fever,  acute  rheumatism  or 
cerebro-spinal  meningitis  was  noted  ;  and  only  2-4  per  cent,  of  these 
patients  got  pneumonia. 

Virchow  believes  that  the  cancerous  are  more  prone  to  inflammatory 
affections,  than  the  non-cancerous. 

With  regard  to  rheumatic  fever,  of  my  267  female  cancer  patients, 
24,  or  8-9 per  cent.,  had  suffered  from  it;  whereas,  of  83  women  with  non- 
cancerous  tumours,  7  had  been  thus  affected,  or  8-4  per  cent. 


Insanity  and  Cancer. 

The  liability  of  insane  persons,  imbeciles  and  idiots  to  cancer,  is 
decidedly  below  the  average  ;  and  they  are  generally  debilitated  and  of 
low  vitality.  The  like  is  true  of  prison  and  workhouse  inmates. 

With  the  advent  of  more  complex  conditions  of  existence  and  greater 
competition,  the  tendency  to  insanity  and  suicide  has  undoubtedly  in- 
creased in  all  modern  communities  ;  and  it  is  especially  among  those  who 
have  failed  in  the  race,  that  these  maladies  are  so  unduly  rampant. 
Hence,  in  our  own  country,  their  increase  has  been  mainly  among  the  poor  ; 
and  men  have  been  affected  more  than  women. 

It  is  beyond  all  question,  that  cancer  is  comparatively  infrequent 
among  the  inmates  of  our  lunatic  asylums,  who  share  this  peculiarity  with 
t  convicts,  paupers,  savages  and  monkeys.  Imbeciles  and  idiots  seem  to  be 
even  less  susceptible,  than  other  demented  persons. 


. 


.ETIOLOGICAL  INDICATIONS  345 

With  regard  to  the  inmates  of  lunatic  asylums,  the  evidence  is  of  a 
very  convincing  kind. 

Some  apposite  data  bearing  on  this  subject,  are  contained  in  the 
appendix  to  the  Fifty-fifth  Report  of  the  Lunacy  Commissioners,  for  the 
year  1900.  Thus,  of  the  8,356  deaths  which  occurred  during  that  year, 
in"the  institutions  under  their  care,  only  186 — or  1  in  45 — were  due  to 
malignant  disease.  Of  these  4,362  were  men,  of  whom  66  died  of  malig- 
nant disease,  or  1  in  66  ;  and  3,994  were  women,  of  whom  120  died  of 
malignant  disease,  or  1  in  33.  The  average  age  of  the  men  at  death  was 
forty-five  years,  and  of  the  women  fifty-one. 

For  comparison  with  these  figures,  we  may  refer  to  the  national 
statistics  for  the  year  1900,  which  show  that  among  the  general  popula- 
tion, thirty-five  years  old  and  upwards,  1  in  15  men,  and  1  in  9  women, 
eventually  died  of  cancer. 

In  a  valuable  essay  on  this  subject  by  H.  Snow,1  it  is  shown  that  of 
5,364  adult  lunatics,  who  died  while  under  treatment  in  the  Han  well 
and  Hitchin  Asylums  (1870-1891),  only  135  died  of  cancer,  or  1  in  39  : 
of  these  2,741  were  women,  of  whom  101  died  cancerous,  or  1  in  27  :  and 
2,623  were  men,  of  whom  34  died  cancerous,  or  1  in  77. 

Of  1,000  insane  women  in  Ontario  asylums,  submitted  to  gynaeco- 
logical examination  by  Hobbs,2  only  3  were  found  to  have  cancer — the 
uterus  being  the  part  affected  in  all. 

In  this  connexion  it  is  interesting  to  note,  that  such  common  non- 
malignant  tumours  as  uterine  myomata  and  ovarian  cystomata,  are  also 
decidedly  rare  among  the  insane,  as  the  researches  of  Wigglesworth,3 
Urquhart,4  Hobbs  and  others  conclusively  prove. 

In  marked  contrast  with  the  rarity  of  cancer  in  insane  women,  is  their 
great  proclivity  to  tubercle — especially  to  phthisis  ;  thus,  during  the  year 
1900,  of  3,994  deaths  among  English  female  asylum  inmates,  no  less  than 
592  were  due  to  phthisis. 


Grief,  Anxiety  and  Mental  Distress. 

Some  authors  attach  great  importance  to  grief,  anxiety  and  mental 
distress,  as  causes  of  cancer  ;  and  they  have  adduced  statistics  in  support 
of  their  belief.  With  regard  to  this,  I  can  only  say,  that  the  majority 
of  cancer  patients  whose  life-history  I  have  investigated,  appeared  to  me 
to  have  been  less  exposed  to  depressing  influences  of  this  kind,  than  most 
women  of  corresponding  age  in  the  general  population.! 

Prison  Inmates  etc. 

Having  seen  it  stated  that  cancer  is  rare  in  prisons,  where  but  little 
animal  food  is  allowed  and  hard  work  is  exacted,  I  have  examined  the 
reports  of  the  commissioners  of  prisons,  to  determine  the  validity  of  this 
matter.  The  data  they  contain  strongly  support  the  contention. 

1  Journal  of  Mental  Science,  October  1891,  p.  548. 

2  American  Journal  of  Obstetrics,  etc.,  February,  1902. 

3  Journal  of  Mental  Science,  January,  1885. 

4  Edinburgh  Medical  Journal,  October,  1901,  p.  315. 


346  THE  NATURAL  HISTORY  OF  CANCER 

Thus,  from  the  reports  for  the  years  1898  and  1897,  it  appears  that  of 
5,915  convicts,  only  3  died  of  malignant  disease  during  those  years,  or 
1  in  1,971.  These  prisoners  were  of  all  ages  above  twenty  years,  hardly 
any  being  under  that  age.  The  three  deaths  from  malignant  disease  all 
took  place  among  the  male  convicts,  of  whom  there  were  5,547,  so  that 
their  cancer  mortality  was  1  in  1,849.  Among  the  368  female  convicts, 
there  was  not  a  single  death  from  malignant  disease. 

In  the  general  population  of  the  same  age  and  during  the  same  years, 
the  mortality  from  malignant  disease  amounted  to  1  in  698 — for  males 
1  in  845  and  for  females  1  in  603. 

Thus  the  mortality  from  malignant  disease  in  the  general  population, 
•/  was  nearly  thrice  as  great  as  that  experienced  by  these  convicts. 

The  prison  population  is  very  prone  to  tubercle,  according  to  Ziemssen, 
nearly  one-half  of  the  total  deaths  being  due  to  this  cause,  the  pulmonary 
form  of  the  disease  being  exceptionally  frequent.  Their  general  death- 
rate  is  also  much  above  the  average,  the  mortality  ratios  for  heart  disease 
and  suicide  being  exceptionally  high. 


Workhouse  Inmates  etc. 

Having  gained  the  impression  by  visiting  workhouses,  that  cancer  is 
of  comparatively  rare  occurrence  among  their  inmates,  I  have  endeavoured 
to  test  the  validity  of  this  impression,  by  reference  to  such  data  as  are 
contained  in  official  reports.  Notwithstanding  the  lavishness  of  the  Poor 
Law  administration  in  this  kind  of  publication,  I  have  found  very  little 
satisfactory  information  available  on  the  subject. 

From  such  crude  data  as  I  have  gathered,  it  may  be  inferred  that  the 
inmates  of  these  institutions  are  less  prone  to  cancer,  than  persons  of  corre- 
sponding age  and  sex  in  the  general  population. 

I  am  indebted  to  Mr.  J.  J.  Simpson,  Clerk  of  the  Bristol  Guardians, 
for  the  following  particulars  :  during  the  years  1901  and  1902,  888  deaths 
took  place  among  the  inmates  of  the  Bristol  workhouses,  and  of  these  54 — 
or  1  in  16 — were  due  to  cancer.  The  majority  of  the  defunct  were  of  post- 
meridian ages,  only  a  few  children  being  included,  and  males  predomi- 
nated to  the  extent  of  about  56  per  cent.  In  the  general  population  for 
the  year  1900,  the  ratio  of  cancer  deaths  to  the  deaths  from  all  causes, 
among  persons  forty-five  years  old  and  upwards,  was  1  in  11  :  during  the 
years  1888-1901,  of  6,791  deaths  at  Guy's  Hospital— mostly  adults— 816 
due  were  to  malignant  disease,  or  1  in  8. 

Dr.  John  R.  Lunn,  medical  superintendent  of  the  Marylebone  Work- 
house Infirmary  (London),  kindly  furnished  me  with  the  subjoined  data, 
as  to  the  prevalence  of  malignant  disease  in  that  institution.  The  figures 
are  based  on  the  average  for  the  three  years  1900-1902.  The  total  deaths 
amounted  to  525  a  year,  of  which  36  were  due  to  cancer,  or  1  in  14  :  of 
270  males  16  died  of  this  malady,  or  1  in  17  ;  and  of  255  females,  20  died 
of  it,  or  1  in  13. 

In  a  previous  chapter,1  I  have  refuted  the  doctrine  of  cancer  being 
morbus  miseria  ;  and  have  shown  its  undue  prevalence  among  the  well- 
to-do. 

1  Chapter  III. 


^TIOLOGICAL  INDICATIONS  347 


Convents  etc. 

Several  Continental  authors  have  reported  that  cancer  is  rare  in  con- 
vents, monasteries  and  similar  institutions,  where  a  frugal  regimen  is 
enforced  ;  according  to  Legrain  and  others,  this  disease  is  almost  un- 
known among  the  Trappist,  Carmelite  and  Carthusian  monks,  who 
abstain  from  flesh  food. 

Dermatoses. 

I  have  often  noticed  on  the  trunk,  face,  upper  limbs  etc.,  of  cancer 
patients,  minute,  pink  telangiectases  ;  but  these  are  also  commonly  seen 
on  the  non-cancerous  of  corresponding  age  and  sex.  A  few  years  ago 
these  minute  spots,  with  which  I  have  been  familiar  for  the  last  quarter  of 
a  century,  were  suddenly  discovered  by  certain  writers,  and  boomed  as 
an  immense  novelty — pathognomonic  of  cancer.  Of  course,  directly  the 
matter  was  closely  looked  into,  it  was  found  impossible  to  maintain 
these  absurd  claims  ;  for  as  Gebele,  Raff  and  Symmers  soon  showed,  these 
vascular  growths  are  just  as  common  in  the  non-cancerous,  as  in  the 
cancerous  ;  and  they  seem  to  be  a  usual  concomitant  of  incipient  sen- 
escence. 

These  telangiectases  were  no  doubt  in  de  Morgan's  mind,  when  he 
referred  to  "  small  outgrowths  of  warty,  vascular  or  dermoid  structure," 
as  often  being  concomitant  with  cancer.1 

I  have,  however,  rarely  seen  warty  or  dermoid  outgrowths  in  this  con- 
nexion ;  nor  have  I  noticed  that  eczema,  psoriasis  or  other  dermatoses, 
often  appear  in  the  course  of  this  disease,  as  Bazin  and  Hardy  allege. 
Herpetic  manifestations  and  chronic  seborrhoea  I  have  rather  more  fre- 
quently seen. 

We  are  indebted  to  the  dermatologists,  and  especially  to  Unna,  for 
recognition  in  comparatively  recent  times  of  a  curious  morbid  condition 
called  acanthosis  nigricans,  which  has  been  found  in  association  with 
intra-abdominal  cancer.2  The  predominant  features  of  this  malady  are 
papillary  and  pigmentar3r  cutaneous  dystrophy,  together  with  hair  and 
nail  lesions,  wasting,  cachexia  etc.  The  clinical  syndrome  has  some  re- 
semblance to  that  met  with  in  "  Addison's  disease,"  from  which,  however, 
it  differs  in  the  rough,  warty,  symmetrical  cutaneous  patches,  wherein  the 
pigmentation  concentres,  while  the  buccal  membrane  is  never  pigmented. 
Although  abdominal  cancer  is  usually  concurrent  with  this  curious 
morbid  condition,  cases  have  been  reported  in  persons  quite  free  from 
cancer  ;  and,  of  course,  it  is  only  a  minority  of  abdominal  cancer  cases 
that  are  thus  complicated. 

Hue  3  has  reported  an  instance,  in  a  woman  aged  forty-five,  the  subject 
of  cancer  of  the  cervix  uteri,  with  symptoms  of  dissemination. 

1  "  The  Origin  of  Cancer,"  1872. 

2  For  further  particulars  reference  may  be  made  to  Couillaud's  essay  ( Gaz.  des  Hdpitaux, 
No.  42, 1892,  p.  413),  and  to  Unna's  book  on  "  The  Histopathology  of  Skin  Diseases,"  1896. 

3  Normandie  Med.,  August  15,  1893. 


348  THE  NATURAL  HISTORY  OF  CANCER 

Paralysed  Parts  and  Cancer. 

1  It  may  be  stated  of  feebly  vitalized  parts  in  general,  that  they  have 
Xbut  little  proclivity  to  cancer.  This  is  specially  true  of  paralysed, 
atrophying,  and  asthenic  parts,  which  hardly  ever  originate  any  kind  of 
tumour,  as  was  long  ago  indicated  by  Broussais.  I  have  never  myself 
seen  a  single  instance  of  malignant  disease,  that  had  originated  under 
such  circumstances  ;  and  Sir  R.  W.  Gowers,  with  his  large  experience  of 
paralytic  affections,  in  answer  to  my  inquiry,  says  that  he  has  never  seen 
malignant  disease  originate  in  paralysed  parts.  Since  most  paralysed 
parts  appertain  to  the  extremities,  which  are  but  little  prone  to  originate 
malignant  disease,  this  proclivity  might  at  first  sight,  be  thought  sufficient 
to  explain  the  immunity.  I  find,  however,  that  about  2  per  cent,  of  all 
malignant  tumours  in  males,  and  1  per  cent,  in  females,  originate  from 
the  extremities  ;  which  is  a  much  greater  proportion  than  is  met  with  in 
the  paralytic,  as  is  evidenced  by  the  almost  complete  absence  of  records 
of  cases  of  malignant  disease  of  paralysed  parts.  I  think  there  can  be 
no  doubt  that  this  immunity  of  paralysed  parts  from  cancer,  is  due  to 
enfeebled  vitality,  rather  than  to  loss  of  hypothetical  neuro-trophic 
influence,  for  reasons  I  shall  have  occasion  to  indicate  in  a  subsequent 
chapter.1 

The  only  instances  of  cancer  originating  in  paralysed  parts  known  to 
me,  are  two  or  three  cases  cited  by  Cruveilhier  2  of  women  who,  having 
had  the  spinal  cord  completely  or  almost  completely  destroyed  in  early 
life,  with  consequent  wasting  of  the  lower  limbs  etc.,  nevertheless,  de- 
veloped fatal  cancer  of  the  uterus,  at  the  usual  age. 

A  case  of  cancer  arising  from  a  perforating  ulcer  of  the  foot,  has  been 
reported  by  Zahn.3 

Menstruation. 

Ever  since  Broussais  wrote,  "  Les  regies  douloureux  annoncent  un 
foyer  d'irritation  dans  le  col  uterin,  et  le  cancer  de  cette  partie  en  eat 
souvent  la  suite  a  1'epoque  qu'on  appelle  critique,  quand  on  n'a  pas 
calme  1' irritation  longtemps  avant  cette  epoque,"  attempts  have  been 
made  to  ascribe  the  great  frequency  of  cancer  of  the  female  reproductive 
organs  to  catamenial  derangements. 

In  this  connexion,  I  have  ascertained  the  following  facts  : 

Of  100  uterine-cancer  patients  under  my  observation,  the  disease  was 
first  noticed : 

Before  the  menopause         „         _  .     in  50 

About  the  time  of  the  menopause  . .          . .  ,,21 

After  the  menopause  . .          . .  j  °  "09 

In  these  patients,  the  mean  age  at  the  first  appearance  of  menstrua- 
tion was  14-5  years,  and  at  its  cessation  46  years. 

The  longest  interval  between  the  menopause,  and  the  onset  of  the 
disease,  was  27  years. 

1  Chapter  XVIII.  -   2  Anat       th    t  j.     u     2g 

3  Arch.  f.  path.  Anat.,  1889,  Bd.  cxvii.,  S.  39. 


^TIOLOGICAL  INDICATIONS    •  349 

Of  104  of  these  patients,  menstruation  had  been  normal  in  96  ;  and 
irregular  only  in  8  (scanty  6,  profuse  2). 

Of  1.232  patients  with  cancer  of  the  cervix  uteri,  Andriezen  and 
Leitch  found  that  only  71,  or  5-8  per  cent.,  had  suffered  from  catamenial 
irregularity. 

Of  87  females  comprised  in  my  list  with  mammary  cancer,  the  disease 
was  first  noticed  : 

Before  the  cessation  of  menstruation        _          _         .»         ...     in  35 
At  about  the  time  of  the  menopause         .  .          .  .          .  .          .  .     ,,  10 

After  the  cessation  of  menstruation  .  .          .  .          .  .          .  .     ,,  42 

In  these  patients  the  catamenia  first  appeared  at  14-5  years,  and 
ceased  at  46-3  years. 

The  following  table  from  Paget  *  shows  the  ages  at  which  menstruation 
ceased  in  400  women,  and  the  ages  at  which  cancer  of  the  breast  was  first 
detected  in  an  equal  number  :  — 


Age8.  jSSraStton.  Onset  of  Cancer- 

Below  35  9  36 


35  to  40 
40  „  45 
45  „  50 
Above  50 


51  62 

140  78 

159  101 

41  -  123- 

400  400 


The  only  catamenial  abnormalities  noticed  in  my  87  breast-cancer 
patients  were,  profuseness  in  6,  irregularity  and  scantiness  in  4. 

These  facts  suffice  to  show  that,  even  in  uterine  and  mammary  cancer 
patients,  the  normality  of  the  catamenial  function  is  seldom  disturbed  ; 
that  it  begins  earlier  and  ceases  later  in  them,  than  in  the  generality  of 
women,  is  simply  an  indication  of  the  more  vigorous  sexual  life  of  cancer 
patients,  which  accords  with  other  facts  ascertained  by  me,  relative  to 
then:  life-history,  such  as  high  fertility,  early  marriage  etc. 

Of  like  import  is  the  fact,  that  the  age  incidence  of  mammary  cancer 
is  very  similar  in  both  sexes,  as  I  have  elsewhere  shown.2 

With  regard  to  gastric  cancer,  as  Brinton  3  long  ago  pointed  out,  the 
very  similar  age  incidence  of  the  malady  in  both  sexes,  shows  that  no 
specific  influence  attaches  to  menstruation  in  this  connexion. 

It  is  thus  evident  that  the  catamenial  function  per  se,  has  no  causal 
connexion  with  the  development  of  cancer. 


Alimentation. 

In  the  course  of  this  work  I  have,  on  many  occasions,  indicated  the 
important  part  played  by  the  conditions  of  existence,  in  determining 
the  incidence  of  cancer.  Among  these  conditions  alimentation  is  an 
important  factor. 

In  the  present  imperfect  state  of  our  knowledge,  it  is  singularly 

1  "Lectures  on  Surgical  Pathology,"  1853,  vol.  ii.(  p.  327. 

2  "  Diseases  of  the  Breast,"  1894,  p.  244. 

3  "  Diseases  of  the  Stomach,"  1864,  p.  225. 


360  THE  NATURAL  HISTORY  OF  CANCER 

difficult  to  determine  the  precise  effect  of  diet  in  this  direction,  in  any 
particular  case  ;  because,  in  all  probability,  its  influence  becomes  appre- 
ciable only  very  slowly,  or  after  more  than  a  single  generation  of  indi- 
viduals has  been  exposed  to  it.  Hence  the  failure  of  the  praiseworthy 
attempt,  of  the  British  Medical  Association's  collective  investigation 
committee1  to  solve  this  problem.  From  returns  collected  by  this 
committee,  it  appears  that  of  194  cancer  patients,  123  had  been  moderate 
eaters,  59  small  eaters,  and  12  large  eaters.  With  regard  to  meat,  99  had 
been  moderate,  78  small,  and  16  large  eaters.  There  was  not  a  single 
strict  vegetarian  among  them  ;  and,  only  a  few,  had  a  bias  to  vege- 
tarianism. 

In  this  connexion,  it  may  be  well  to  recall  the  fact,  that  although 
cancer  is  remarkably  rare  in  vegetarian  communities,  yet  complete 
exemption  cannot  be  claimed  for  such  ;  and  the  like  is  true  of  herbivorous, 
as  compared  with  carnivorous  animals.  In  spite  of  these  facts,  which 
indeed  are  only  such  as  might  have  been  expected  from  the  essential 
nature  of  the  problem,  there  cannot  be  the  slightest  doubt — in  face  of  the 
overwhelming  evidence  I  have  adduced  in  the  course  of  this  work — that 
the  incidence  of  cancer  is  largely  conditioned  by  nutrition. 


Salt. 

The  presence  of  salt  in  animal  tissues  is  so  universal,  that  it  may  be 
regarded  as  indispensable  to  their  constitution,  functional  integrity,  and 
nutrition  ;  but,  in  general,  flesh-eating  animals  find  a  sufficient  supply 
of  it,  in  the  alimentary  substances  on  which  they  subsist,  and  they 
dislike  any  artificial  addition  thereto.  It  is  in  herbivora,  that  the  craving 
for  additional  salt  is  so  common.  Similarly  with  mankind,  it  is  among 
the  vegetarians  that  the  salt  consumption  ab  extra  is  greatest ;  and 
Bunge  regards  the  continued  use  of  vegetable  foods,  as  being  the  cause 
of  the  demand  for  salt  as  a  condiment.  This  relationship  was  long  ago 
indicated  by  Darwin,2  who  says  of  the  South  American  people  :  "  The 
Indians  eat  much  salt,  their  children  sucking  it  like  sugar.  This  habit 
is  very  different  from  that  of  the  Spanish  Gauchos  (great  meat  eaters) 
who,  leading  the  same  kind  of  life,  eat  scarcely  any  salt.  According  to 
Mungo  Park,  it  is  people  who  live  on  vegetable  food,  who  have  an 
unquenchable  desire  for  salt." 

Cancer  is  commoner  in  Argentina — which  comprises  the  pampas 
region  inhabited  by  the  Gauchos,  who  for  months  subsist  entirely  on 
beef,  and  never  touch  salt — than  in  other  parts  of  South  America.  On 
the  other  hand,  among  the  natives  of  Egypt,  who  are  of  vegetarian 
habits,  and  consume  immense  quantities  of  salt,  cancer  is  almost 
unknown,  as  I  have  shown  in  a  previous  chapter.3 

In  like  manner  with  our  domesticated  animals,  cancer  is  of  most 
frequent  occurrence  among  dogs,  which  are  carnivorous,  but  avoid 
artificially  salted  food  ;  and  cancer  is  also  common  among  cats,  which 
have  similar  habits. 


*  British  Medical  Journal,  February  26,  1887. 
Naturalist's  Journal  of  Researches,  etc.,  1891,  p.  139. 


3  Chapter  II. 


.ETIOLOGICAL  INDICATIONS  351 

Considerations  of  this  kind,  which  may  easily  be  multiplied,  seem  to 
me  to  centra-indicate  Braithwaite's  theory,1  that  an  excess  of  salt  in  the 
diet  is  a  factor  in  the  causation  of  cancer. 


Alcohol. 

Meat-eating  communities  are,  as  a  rule,  also  alcohol-consuming. 
There  is,  however,  no  evidence  to  show  that  the  habitual  consumption  of 
alcoholic  liquors  per  se,  in  any  way  predisposes  to  cancer. 

No  doubt  the  last  half-century  has  witnessed  great  increase  in 
alcoholism  and  intemperance ;  and  indulgence  of  this  kind  has  now 
certainly  attained  harmful  proportions.  But,  because  this  access  of 
intemperance  has  coincided  with  augmented  cancer  mortality,  it  does 
not  necessarily  follow  that  this  is  a  legitimate  basis  for  inferring  aetiological 
connexity  ;  and,  against  any  such  conclusion,  I  would  urge  the  following 
considerations  : — 

1.  As  the  result  of  special  inquiries  into  the  life-history  of  female 
cancer  patients,  based  upon  the  analysis  of  several  hundred  cases,  I  have 
shown  that  these  persons  had  almost  invariably  led  regular,  sober  and    < 
industrious    lives ; 2    and    Butlin's    collective    investigation    report,3  on 
women  with  mammary  cancer,  is  of  similar  import. 

2.  With  regard  to  male  cancer  patients,  Isambard  Owen  4  has  shown 
that  of  116 — aged  from  forty  to  sixty-five — who  had  died  of  malignant 
disease,  50-76  per  cent,  had  been  total  abstainers  or  habitually  temperate, 
25-7  per  cent,  had  been  "  careless  "  drinkers,  and  22-3  per  cent,  had  been 
decidedly  intemperate.     Newsholme,5  however,  concludes  that,  among 
men,  the  cancer  mortality  for  abstainers  per  1,000,  is  0-95,  and  for  non- 
abstainers  1  -32  ;  but,  as  he  points  out,  not  much  reliance  is  to  be  placed 
in  these  results,  owing  to  paucity  of  data  and  other  sources  of  fallacy. 

3.  It  accords  with  the  foregoing  conclusion,   that  the  increase  in 
alcoholism  has  been  greater  among  women,  than  among  men  ;  whereas, 
with  the  increased  cancer  mortality,  it  is  just  the  converse. 

4.  It   has   been   noticed   that   hotel-,    restaurant-    and   inn-keepers, 
brewers    and    commercial    travellers,    who    have    special    facilities    for 
obtaining  alcoholic  drinks,  have  a  high  cancer  mortality  :  but,  that  this 
is  due  to  some  other  cause  than  alcoholism,  is  evident  from  the  fact  that 
printers,  compositors,  pressmen,  paper-makers,  iron  and  steel  workers — 
who  are  notorious  for  their  drunken  habits — are,  however,  less  prone  to 
cancer  than  any  other  workers  in  the  whole  community. 

5.  In  Bavaria  and  Saxony,  the  cancer  mortality  is  very  high  ;  and 
Wolff  ascribes  this  to  the  beer-drinking  habits  of  the  natives  ;  but,  as 
against  this,  I  should  point  out  that  in  Norway,  Sweden  and  Denmark, 
where  the  consumption  of  alcoholic  liquor  is  small  owing  to  restrictive 
legislation,  the  cancer  mortality  is  even  higher  than  in  Bavaria  and 
Saxony.     Similarly  with  regard  to  wine-drinking  countries,  it  is  only 

1  Lancet,  December  7,  1901. 

2  Middlesex  Hospital  Surgical  Report  for  1888  (by  the  author). 

3  British  Medical  Journal,  February  26,  1887,  p.  59. 

*  Ibid.,  January  23,  1888.  *  British  Medical  Journal,  1903,  vol.  ii.,  p.  1529. 


352  THE  NATURAL  HISTORY  OF  CANCER 

necessary  to  recall  the  great  rarity  of  cancer  among  the  inhabitants  of 
the  Mediterranean  littoral,  Spain  and  Italy,  where  wine-drinking  is 
uinversal,  to  realize  that  this  custom  has  nothing  to  do  with  the  incidence 
of  cancer'.  Of  similar  import  is  the  rarity  of  cancer  among  the  whisky- 
drinking  peasants  of  the  "wild  west"  of  Ireland.  Examples  of  this 
kind,  which  might  easily  be  multiplied,  suffice  to  show  that  neither 
beer,'  wine  nor  spirit  drinking,  entails  proclivity  to  cancer. 

6.  Of  like  significance  is  the  fact,  that  while  alcoholism  is  at  its 
maximum  in  the  slums  of  our  large  towns,  it  is  just  in  these  localities, 
that  the  cancer  mortality  is  the  lowest. 

From  the  ensemble  of  these  indications  we  may  safely  conclude,  that 
persons  addicted  to  alcoholism — whether  in  the  form  of  beer,  wine  or 
'     spirit — have  no  special  proclivity  to  malignant  tumours. 


Water. 

If  it  were  true,  that  "  evidence  produces  conviction  as  much  by  the 
frequency  of  its  repetition  as  by  its  weight,"  then  we  should  be  obliged  to 
believe  that  cancer  is  often  spread  through  the  agency  of  drinking-water. 

Even  as  long  ago  as  1809,  it  was  alleged  by  William  Lambe,1  that  all 
drinking-water  was  contaminated  by  arsenic,  which  caused  those  who 
drank  it  to  become  cancerous  ;  hence,  he  advocated  the  use  of  arsenic- 
free  distilled  water  for  the  cure  of  cancer,  and  he  narrates  in  detail  many 
striking  "  cures  "  effected  in  this  way. 

It  was  probably  owing  to  the  prevalence  of  ideas  of  this  kind,  that 
such  strenuous  opposition  was  manifested  to  the  New  River  Company ; 
when,  in  the  early  part  of  the  nineteenth  century,  it  substituted  iron 
pipes  for  the  bored  elm-trunks,  that  had  previously  been  used  for  con- 
veying drinking-water  to  London ;  the  opposition  gravely  alleging — as 
we  learn  from  a  correspondent  in  the  Standard  2 — that  the  consumption 
of  water  conveyed  through  iron  pipes  would  produce  cancer. 

Recently,  the  prevalence  of  cancer  in  the  volcanic  plateau,  which 
constitutes  the  Ballarat  gold-field,  has  been  ascribed  by  J.  H.  Webb,3 
to  the  drinking  of  rain-water,  that  had  been  stored  in  galvanized  iron  or 
cement-lined  tanks  etc. 

In  like  manner,  it  has  lately  been  suggested  by  J.  Hutchinson,  that 
cancer  is  caused  by  arsenic-contaminated  beer. 

In  such  instances  as  the  foregoing,  the  incriminated  element  generally 
is,  a  small  quantity  of  arsenic  dissolved  in  the  water.  With  regard  to 
this,  it  may  be  stated  that  in  Styria,  where  arsenic  eating  is  said  to 
prevail,  the  cancer  mortality  is  by  no  means  high  ;  and,  in  this  country, 
among  those  engaged  in  industrial  occupations  involving  contact  with 
arsenic,  no  undue  cancer  mortality  has  been  noted.  In  short,  there 
seems  to  be  no  sufficient  basis  for  the  belief,  that  the  ingestion  of  arsenic 
is  a  cause  of  cancer. 

In  other  instances,  water  has  been  alleged  to  cause  cancer,  through 

1  Reports,  etc.,  on  the  Effect  of  a  Peculiar  Regimen  on  Cancer,  London,  1809. 

2  J.  W.  Ford  in  the  Standard  of  May  1,  1899. 

3  Lancet,  1901,  vol.  ii.,  p.  976. 


.ETIOLOGICAL  INDICATIONS  353 

its  harbouring  micro-organisms  or  other  organic  impurities  (Arnaudet, 
Behla  etc.)  ;  but  these  allegations  have  never  been  substantiated. 

Equally  destitute  of  foundation  are  the  assertions  that  cancer  is 
caused  by  the  softness  or  hardness  of  drinking-water,  by  its  contamina- 
tion with  sewage  etc.  ;  and  the  claims  of  curative  properties  for  hard,  soft, 
and  various  mineral  waters,  are  just  as  unsubstantiated. 

In  short,  I  have  failed  to  find  any  valid  evidence,  that  the  incidence 
of  cancer  is  in  any  way  dependent  upon  the  supply  of  drinking-water. 


Late  Marriage,  Decline  in  the  Birth-Rate,  Celibacy  etc. 

Under  favourable  conditions,  the  population '  of  a  country  has  been 
known  to  double  itself — independently  of  immigration — in  twenty-five 
years  or  less  ;  but,  in  modern  communities,  such  a  rate  of  increase  is  now 
never  met  with,  and,  in  our  own  country,  the  last  doubling  of  the  popula- 
tion has  taken  nearly  sixty  years.  It  is  thus  obvious  that,  in  all  modern 
communities,  the  reproductive  capacity  is  enormously  repressed.  More- 
over, this  repression  is  much  greater  among  the  wealthy  and  well-to-do 
classes,  than  among  the  rest  of  the  community,  as  Bertillon  has  shown  ; 
thus,  while  the  birth-rate  per  1,000  women  of  the  London  population — 
aged  fifteen  to  fifty — for  the  rich  was  only  75,  the  corresponding  figure 
for  the  poor  was  143.1  In  all  modern  occidental  communities,  there  has 
been  a  marked  decline  in  the  birth-rate,  during  the  last  half-century, 
which  is  still  in  progress  ;  and  this,  of  course,  implies  late  marriages,  with 
lessening  fertility  thereof,  and  increasing  celibacy. 

Social  scientists  have  been  much  exercised  to  explain  this  greatly 
diminished  fertility  of  wealthy  modern  communities,  and  the  general 
tendency  has  been  to  ascribe  it  to  the  wholesale  adoption  of  "  positive  " 
checks  ;  but,  it  seems  to  me  much  more  likely  that  most  of  it  is  due  to 
quite  other  causes,  viz.,  to  a  diet  unduly  rich  in  proteids.  In  the  organic 
world  in  general,  it  has  been  clearly  proved  that  an  abundant  supply  of 
nutriment  everywhere  causes  great  diminution  of  gamogenetic  fertility  ; 
and,  in  our  country,  as  I  have  indicated,  the  falling  off  in  this  respect  has 
been  chiefly  among  the  well-to-do.  This  explanation  of  the  diminished 
fertility  of  well-to-do  communities,  was  long  ago  advanced  by  Doubleday  ;2 
and  it  finds  a  certain  amount  of  support  in  experiments  on  animals, 
for  rats  fed  on  meat  diet  have  been  found  to  experience  great  diminution 
in  their  reproductive  capacity  and  fertility.  It  is  not  improbable,  there- 
fore, that  diet  plays  an  important  part  in  the  increase  of  cancer,  the 
decrease  of  tubercle  and  the  diminution  of  the  birth-rate. 

As  I  have  elsewhere  indicated,3  the  increase  of  cancer  among  women 
cannot  be  ascribed  to  their  fecundity  ;  for,  in  addition  to  the  facts 
there  adduced,  it  may  also  be  mentioned,  that  while  the  marriage-rate 
has  of  late  increased,  the  birth-rate  has  markedly  declined ;  so  that  the 
fecundity  of  modern  women  has  diminished,  while  their  proclivity  to 
cancer  has  increased. 

1  For  further  details,  vide  Chapter  II.,  p.  26. 

2  Doubleday's  important  discovery  was  rejected  by  John  S.  Mill,  who  was,  however, 
more  of  a  logician  and  metaphysician  than  a  biologist  or  social  scientist ;  indeed,  Mill's 
lack  of  biological  knowledge  is  painfully  apparent  in  all  his  works.  3  Chapter  XI. 


354  THE  NATURAL  HISTORY  OF  CANCER 

Of  course,  such  changes  in  social  conditions  as  those  with  which  we 
are  here  concerned,  have  been  attended  with  concurrent  alterations  in 
the  age  constitution  of  the  population,  with  survival  of  greater  numbers 
to  the  cancer  age  ;  but,  only  a  very  small  part  of  the  increased  cancer 
mortality— which  has  been  estimated  at  ^ — can  be  thus  accounted  for. 

Occupation  etc. 

Although  it  cannot  be  said  that  persons  of  any  rank  or  station  in  life 
are  exempt  from  cancer  ;  there  are,  nevertheless,  some  remarkable  differ- 
ences in  the  incidence  of  the  disease,  among  the  various  social  strata.  I 
have  already  had  occasion  to  point  out  the  much  greater  prevalence  of 
cancer  among  the  well-to-do,  and  among  the  agricultural  community, 
than  among  the  less  prosperous  of  the  industrial  classes  in  our  great 
towns,  as  well  as  its  comparative  rarity  among  paupers,  lunatics,  and  the 
prison  population. 

Perhaps  the  most  significant  result  hitherto  attained  by  statistical 
investigation  of  this  subject,  is  that  arrived  at  by  Dr.  Tatham,1  who 
found  that  the  mortality  from  cancer  during  the  decennium  1881-1890, 
was  more  than  twice  as  great  among  well-to-do  men  having  no  specific 
occupation,  as  among  occupied  males  in  general,  the  respective  cancer 
mortality  ratios  being  96  for  the  former  and  only  44  for  the  latter. 

In  like  manner,  Aschoff  has  shown  that,  in  the  Berlin  population, 
cancer  was  of  most  frequent  occurrence  among  persons  of  independent 
means,  living  on  their  income  or  pension. 

All  statistics  shoAv  that  printers,  compositors  and  pressmen  experience 
a  very  low  cancer  mortality,  while  their  death-rate  from  tubercle  and  their 
general  mortality,  are  both  very  much  in  excess  of  the  average  ;  and  this 
class  is  notoriously  one  of  the  most  intemperate  as  regards  alcohol  etc.,  in 
all  modern  communities. 

According  to  the  Twelfth  United  States  Census  Report,  for  the  year 
1900,  the  cancer  death-rate  for  this  class  was  22  per  100,000  living,  the 
corresponding  figure  for  pulmonary  tubercle  being  435. 

Another  class  of  workers  but  little  prone  to  cancer,  are  the  miners — 
especially  coal-miners — and  quarrymen  ;  the  United  States  statistics  for 
this  class  show  a  cancer  death-rate  of  33  ;  and  a  phthisis  death-rate  of  120. 

AschofFs  Berlin  data,  place  the  miners  next  to  the  printers,  in  respect 
to  comparative  immunity  from  cancer. 

In  England,  there  are  few  districts  where  cancer  is  less  prevalent, 
than  in  the  great  colliery  centres  of  Derbyshire,  South  Wales,  Durham 
and  Lancashire  ;  and  in  the  mining  and  quarrying  districts  of  Cornwall, 
North  Wales  and  elsewhere,  very  low  cancer  death-rates  also  prevail. 

With  regard  to  the  very  high  mortality  of  chimney-sweeps  from 
cancer,  as  shown  by  the  English  national  statistics,  I  am  inclined  to  think 
that  the  calculation  is  based  on  too  small  a  number  of  cases  to  give  a 
reliable  average,  and  is  otherwise  defective  ;  at  any  rate,  nothing  of  the 
kind  has  been  noted  in  the  United  States,  nor  in  Continental  European 
countries. 

1  Supplement  to  Registrar-General's  Fifty-fifth  Annual  Report,  1897. 


.ETIOLOGICAL  INDICATIONS  355 

Moreover,  I  have  found  that  cancer  of  the  corresponding  anatomical 
part  in  women — the  vulva — is  nearly  as  common  as  cancer  of  the  scrotum 
in  males  :  for,  of  4,628  primary  cancers  in  females,  104  were  of  the  vulva 
or  2-2  per  cent.  ;  while  of  2,669  cancers  in  males,  76  were  of  the  scrotum 
or  2-8  per  cent. 

In  general,  cancer  is  comparatively  infrequent  among  the  working 
classes  of  our  large  towns,  especially  in  the  great  industrial  centres,  and 
among  the  cotton  and  textile  operatives,  iron  and  steel  workers  etc. 

On  the  other  hand,  among  the  well-to-do,  the  cancer  mortality  is 
certainly  much  in  excess  of  the  average. 

Thus,  among  the  leisured  and  professional  classes,  the  United  States 
Census  Report — for  1900 — shows  that  high  cancer  death-rates  prevail, 
especially  for  the  clergy,  merchants,  brewers,  hotel  and  restaurant  keepers, 
hotel  servants,  butchers,  agriculturalists,  sailors,  commercial  travellers, 
carpenters  etc. 

Workers  in  soot,  tar,  paraffin,  arsenic  etc.,  are  specially  prone  to 
certain  forms  of  cutaneous  cancer ;  and  it  has  been  reported,  that  those 
employed  in  particular  cobalt  and  nickel  mines,  are  prone  to  quasi- 
malignant  pulmonary  disease. 

There  are  good  reasons  for  believing  that  farm  labourers,  gardeners, 
sailors,  and  those  who  follow  out-of-door  occupations,  are  unduly  prone 
to  cancer  of  the  lower  lip. 

Of  36  men  with  cancer  of  the  lower  lip  who  came  under  my  observation 
in  London  hospital  work,  5  were  farm  labourers,  5  general  labourers, 
3  sailors,  2  bricklayers,  and  1  each  as  follows  : — saddler,  cowman,  black- 
smith, stoker,  worker  in  a  paper  factory,  piano-maker,  sewerman,  bailiff, 
gardener,  brazier,  carpenter,  gas-fitter,  costermonger,  carman,  com- 
mercial agent,  boatman,  waiter,  soldier,  fireman  and  groom. 

The  large  proportion  of  patients  engaged  in  out-of-door  occupations 
comprised  in  this  list,  is  very  remarkable  ;  especially  when  regard  is  had 
to  the  sedentary  occupations  followed  by  the  great  bulk  of  the  London 
population,  whence  these  cases  were  drawn. 

With  regard  to  the  influence  of  occupation  on  the  liability  of  women 
to  malignant  disease,  perhaps  the  most  significant  item  hitherto  elicited. 
is  that  brought  out  by  the  United  States  Census  Report  for  1900,  which 
shows  that  domestic  servants  are  unduly  prone  to  cancer  ;  thus,  during 
the  age-period  forty-five  to  sixty-five,  their  mortality  from  this  cause  was 
double  the  average  ;  and,  at  ages  above  sixty-five,  it  was  triple  the  average. 
Cancer  death-rates,  above  the  average,  were  also  noted  among  nurses, 
midwives  and  school-teachers. 

With  regard  to  the  female  hospital  patients  with  cancer,  under  my 
observation,  most  of  them  had  been  supported  entirely  by  their  hus- 
bands' earnings  ;  but  such  of  them  as  had  worked  for  their  living — 
whether  married,  widowed  or  single — had  followed  the  following  occupa- 
tions in  142  cases  : — thus,  domestic  service  62  (cook  17,  charwoman  13. 
housekeeper  6,  other  forms  of  domestic  service  26)  ;  needlework,  dress- 
making etc.  28 ;  sick  nurse  or  midwife  16  ;  laundry  16 ;  governess  or 
school-teacher  7  ;  factory  7  ;  shop  assistant  4 ;  barmaid  and  actress,  of 
each  1. 

23—2 


CHAPTER    XVII 
FAMILY  HISTORY 

THE  problem  of  heredity,  in  relation  to  disease,  has  hitherto  seldom  been 
viewed  in  a  right  light.  The  fundamental  error  has  been  the  tacit  assump- 
tion that  pathological  states,  like  normal  conditions,  are  almost  invariably 
inherited.  It  has  been  overlooked  that  the  predispositions  of  the  organism 
are  to  normality  ;  and  that  diseases — like  other  recently  acquired  charac- 
ters— tend  to  disappear  under  suitable  environmental  conditions.  In 
fact,  so  great  is  the  preponderating  influence  of  the  previous  ancestral 
balance,  that  diseases  are  never  reproduced  in  the  offspring,  with  the 
same  constancy  and  regularity  that  normal  conditions  are.  Hence,  even 
in  families  where  hereditary  morbid  tendencies  are  the  strongest,  most 
of  the  members  usually  escape ;  and  this  is  notably  the  case  with 
cancer. 

Nevertheless,  it  is  undoubtedly  true  that  the  descendants  of  a  family 
in  which  a  new  morbid  variation  has  appeared  are,  other  things  being 
equal,  more  likely  to  vary  again  in  a  similar  way,  than  are  persons  whose 
relatives  have  never  manifested  such  variation.  This  principle,  as  I  shall 
proceed  to  show,  is  also  applicable  to  cancer. 

Thus,  in  Broca's  celebrated  case  of  multiple  family  cancer  to  be 
presently  cited,  of  the  twenty-six  descendants  of  Madame  Z.  who 
attained  or  exceeded  the  age  of  thirty,  fifteen  died  of  cancer  ;  whereas  the 
cancer  proclivity  for  the  same  number  of  persons  of  the  general  population 
at  the  corresponding  period  of  life,  is  considerably  less  than  one  ;  that  is 
to  say,  the  liability  to  the  disease  was  here  increased  more  than  fifteen 
times  by  the  influence  of  heredity. 

No  doubt  it  is  a  difficult  thing  to  define  scientifically,  the  precise 
nature  of  the  essential  basis  on  which  pathological  heredity  depends  ;  but, 
for  present  purposes,  it  will  suffice  if  we  adopt  Hughlings  Jackson's  con- 
ception :  "  To  similar  causes  there  are  in  those  similarly  constituted — like 
members  of  families — similar  modes  of  physiological  and  pathological 
reaction."  If  we  knew  more  about  the  circumstances  under  which 
predisposition  to  cancer  arises,  the  problem  of  prevention  would  be 
simplified  ;  for  then  we  might  be  able  to  determine  how — by  cross  breeding 
or  otherwise — to  convert  morbidly-tending  into  healthy  stocks.  What, 
then,  is  the  predisposition  most  likely  in  breeding,  to  counteract  a  ten- 
dency to  cancer  ?  To  this  it  may  be  answered,  according  to  my  belief, 
that  persons  of  a  spare  physical  type,  of  medium  weight  and  height, 
active  disposition,  fond  of  open-air  life  and  exercise,  and  getting  plenty 
of  it,  with  well-developed  sexual  system,  and  concomitant  frugality  of 

356 


FAMILY  HISTORY  357 

habits — especially  in  respect  to  food — and  above  all,  free  from  any 
cancerous  or  tuberculous  predisposition  and  proclivity  to  obesity ;  such 
are,  I  think,  the  types  most  likely  in  breeding,  to  counteract  a 
tendency  to  cancer. 

According  to  Hippocrates,  to  prevent  the  diseases  to  which  indi- 
viduals are  hereditarily  predisposed,  we  ought  to  change  their  constitu- 
tion ;  and  this  is  to  be  effected,  by  bringing  them  up  under  different 
conditions  of  existence,  from  those  in  which  their  parents  have  lived. 
In  the  preventive  treatment  of  cancer,  this  indication  should  not  be 
neglected. 

In  referring  to  this  matter  Darwin  says  :  "  The  increased  vigour 
resulting  from  cross-fertilization,  is  allied,  in  the  closest  manner,  to  the 
advantage  gained  by  change  of  conditions.  So  strongly  is  this  the  case, 
that  in  some  instances  cross-fertilization  gives  no  advantage  to  the 
offspring,  unless  the  parents  have  lived  under  slightly  different  conditions. 
So  that  the  really  important  thing  is,  not  that  two  individuals  of  different 
blood  shall  unite,  but  two  individuals  who  have  been  subjected  to  different 
conditions." 

Very  conflicting  are  the  views  now  prevalent  as  to  the  hereditability 
of  the  disease.  These  contradictory  opinions  are  no  doubt  largely 
attributable,  to  the  prevailing  confusion  in  the  fundamental  conceptions 
of  heredity.  As  I  cannot  here  enter  on  the  burning  question  of  Weis- 
mannism  versus  Darwinism,  it  must  suffice  for  me  to  state  ;  that  I  regard 
the  distinction  between  somatic  and  germ  cells,  on  which  Weismann's 
theory  is  based,  as  artificial.  As  I  have  previously  indicated,  the  repro- 
ductive properties  manifested  by  somatic  and  germ  cells  are  the  same  in 
kind,  and  they  differ  only  in  degree.  I  also  believe  that  acquired  char- 
acters are  hereditable.  In  weighing  this  question,  Weismann  has  ignored 
the  evidence  deiived  from  the  study  of  disease,  which  is  incompatible  with 
his  theory  and  conclusions,  as  the  facts  to  be  cited  in  this  chapter  alone 
suffice  to  show. 

The  first  principles  being  in  this  unsettled  state,  it  will  be  well  to  pass 
at  once  to  the  consideration  of  the  cardinal  facts. 

As  Karl  Pearson  has  remarked :  "  It  is  difficult  to  conceive  that 
longevity  and  general  health  can  be  inherited,  if  the  tendencies  to  par- 
ticular diseases  do  not  run  in  families."1 

To  my  mind,  the  hereditability  of  cancer  is  more  conclusively  proved,, 
by  the  occurrence  of  several  instances  of  the  disease  in  certain  families, 
in  one  or  in  successive  generations,  than  by  any  other  considera- 
tion. 

Although  such  coincidences  may  not  invariably  amount  to  absolute 
proof  of  hereditary  transmission  ;  yet,  when  we  see  families  thus  affected, 
in  which  tumours  of  this  kind  develop  in  the  same  organs,  and  that  during 
several  generations,  it  seems  to  me  unscientific  to  deny  the  hereditability 

1  As  an  example  of  this,  reference  may  be  made  to  the  transmission  of  deaf-mutism. 
Buxton's  researches  show  that  of  303  marriages,  in  which  both  of  the  contracting  parties 
were  deaf  and  dumb,  one  in  twenty  of  the  offspring  were  similarly  affected  ;  and  that  of 
310  deaf-mutes  married  to  hearing  people,  the  proportion  of  deaf  and  dumb  among  the 
offspring  was  1  in  135.  In  the  general  population  at  this  period  the  proportion  of  deaf- 
mutes  was  about  1  in  1,600.  Independent  investigations  since  carried  out  by  Mygge, 
Hartmann  and  others  have  fully  confirmed  Buxton's  results. 


358  THE  NATURAL  HISTORY  OF  CANCER 

of  the  disease,  especially  when,  as  is  frequently  the  case,  these  morbid 
manifestations  are  exclusively  confined  to  one  side  of  the  family  or  to 
one  sex. 

Such  cases  show  that  there  is  inherited  a  special  abnormality  of 
organs,  tissues,  and  cells,  which  manifests  itself  in  their  aptness  to  beget 
cancer.  To  account  for  this  we  may  suppose  that,  just  as  an  inherited 
capacity  for  a  certain  regularity  and  amount  of  growth,  is  a  quality 
inherent  to  all  normally  evolving  cells  ;  so  irregularity  of  growth  may  also 
become  hereditable,  in  cells  that  have  once  acquired  the  habit  of  aberrant 
propensities.  In  the  one  case,  as  in  the  other,  it  is  to  the  persistence  of 
impressions  in  the  living  protoplasm,  that  we  must  look  for  the  explana- 
tion of  this  phenomenon.  Hence,  when  we  speak  of  hereditary  trans- 
mission in  these  cases,  what  is  meant  is,  that  such  abnormalities  of  growth 
are  but  the  manifestations  of  long  antecedent  physical  impressions.  "  It 
appears  to  me  almost  certain,"  says  Darwin,  "  that  the  characters  of  the 
parents  are  '  photographed '  on  the  child,  by  means  of  material  atoms 
derived  from  each  cell  of  both  parents,  and  developed  in  the  child." 

The  problem  of  heredity  is,  in  fact,  the  problem  of  the  manner  of 
distribution  of  characters  among  the  germ- cells. 

Such  instances  of  multiple  family  cancer,  as  the  subjoined,  prove  the 
hereditability  of  the  disease  ;  for,  it  is  obviously  impossible  that  those 
thus  affected  could  have  acquired  the  malady  from  a  common  source  of 
infection,  and  concurrences  of  this  kind  cannot  be  interpreted  as  being 
fortuitous. 

Breast. 

1.  The  following  case  recorded  by  Broca,i  is  the  most  complete  of 
its  kind  that  has  ever  been  published  ;  and  this  is  mainly  due  to  the  fact, 
that  the  family  included  an  eminent  physician  among  its  members,  who 
furnished  the  particulars  as  under  : 

First  Generation.— Madame  Z.  died  of  cancer  of  the  breast,  aged 
sixty.  She  left  four  daughters — A,  B,  C  and  D. 

Second  Generation. — The  four  daughters  of  Madame  Z. 

(1)  Madame  A  died  of  cancer  of  liver,  aged  62. 

(2)  "        B       »»  „  „  43  • 

(3)  „         C      „  „  breast     „     51. 
(*)        "         D      »             „  „         „     54.. 

Third  Generation.— Madame  A.  had  three  unmarried  daughters, 
still  alive  and  well,  aged  sixty-eight,  seventy-two,  and  seventy-eight 
years. 

Madame  B.  had  five  daughters  and  two  sons.  First  son  died — not 
aicerous— at  the  age  of  twenty-eight,  and  without  issue.  Second  son 
Jd  of  cancer  of  stomach,  aged  fifty-four,  and  without  issue. 

First  daughter  died  of  cancer  of  breast,  aged  35 

Second     „  „  <>*  t    ,~^ 

Third        „  "      « I    T*  (All  unmarried,  and 

£°f^th  ••     '.',     ;:     liver,  ;;  S£$j  ^-t^- 

_ """        ••  »    not  cancerous,  „      60  Married,  but  no  issue. 

"  Trait e  des  Tumeurs,"  1866,  t,  i.,  p.  151. 


First  daughter  died  of  cancer  of  the  breast, 
aged   37,   leaving  two   sons  and   three  < 


FAMILY  HISTORY  359 

Madame  C.  had  five  daughters  and  two  sons  : 

First  son  died  in  the  army  without  issue. 

I"  He  had  a  son  who  died  paraplegic,  aged  18, 

Second  son  alive  and  well,  aged  72.  j          and  an  only  daughter,  who  is  alive 

[         and  well,  aged  24,  unmarried. 
First  son,  aged  58,  alive  and  well.     He  has 
three  sons  alive  and  well,  the  oldest 
aged  30. 
Second  son  died  young,  abroad,  without 

issue. 
First    daughter   died    in    child-bed,   aged 

about  28. 

Second   daughter   died   of   cancer   of   the 
breast,  aged  49.     She  left  two  daugh- 
ters.     Both  are  alive  and  well ;   the 
elder  is  22. 
Third  daughter  died  of  phthisis,  aged  41. 

Second  daughter  died,  aged  40,  of  cancer  of\c,     ,  ,, 

the  breast  j-She  left  an  only  son,  who  is  alive  and  well. 

Third  daughter  died,  aged  47,  of  cancer  of\TT  .    , 

uterus,  / unn       iecl- 

the  breast  '   J-She  left  two  sons,  who  are  alive  and  well. 

Fifth  daughter  died,  aged  61,  of  cancer  of\  rT  .    , 

liver.  )  Unmarried. 

Madame  D.  had  an  only  son,  who  is  alive  and  well,  aged  seventy. 

2.  In  a  family  known  to  Sibley,1  the  mother  and  her  five  daughters 
all  died  of  cancer  of  the  left  breast. 

3.  Velpeau  2  met  with  cancer  of  the  breast,  in  a  mother  and  her  three 
daughters. 

4.  Korteweg  3  has  seen  the  same  malady  in  grandmother,  mother  and 
daughter. 

5.  Gibson  4  met  with  it  in  four  sisters ;  and  Moore  5  also  knew  of  a 
family,  in  which  all  the  sisters  had  cancer  of  the  breast. 

6.  Of  14  members  of  2  related  families  known  to  Iterson,6  8  certainly 
died  of  cancer  (5  of  the  female  breast),  and  3  others  probably. 

7.  A  woman,  aged  thirty-seven,  came  under  my  observation  with 
cancer  of  the  breast,  who  had  lost  two  sisters  also  from  cancer  of  the 
breast,  and  a  brother  who  died,  aged  thirty,  of  "  tumour  of  the  back." 
This  patient's  father  died,  aged  forty- two,  of  cancer  of  the  breast ;  and 
of  his  two  sisters,  one  died,  aged  fifty-two,  of  cancer  of  the  breast,  and 
the  other  of  cancer  of  the  liver. 

8.  J.  H.  Power  7  has  reported  the  case  of  a  man,  whose  right  breast  had 
been  amputated  for  cancer,  with  subsequent  recurrence  in  the  axilla,  whose 
father  died  of  cancer  of  the  right  breast.     Of  this  patient's  two  brothers 
and  eight  sisters,  all  but  two  of  the  latter — who  died  young — were  the 
victims  of  cancer.     Of  his  brothers,  the  elder  died  of  "  cancer  of  the 

Transactions  of  the  Medico-Chirurgical  Society  of  London,  1859,  vol.  xlii.,  p-  110. 

"  Traitedes  maladies  du  sein,"  1858,  p.  685. 

"  Veroffentlichungen  des  Comitees  fiir  Krebsforschung,"  1902. 

Cited  by  S.  D.  Gross  hi  his  "  System  of  Surgery,"  1882,  6th  edit.,  vol.  L,  p.  242. 

"  Antecedents  of  Cancer,"  1865,  p.  16. 

Veroffentlichungen  des  Comitees  fiir  Krebsforschung,"  1902. 

British  Medical  Journal,  1898,  vol.  ii.,  p.  154. 


360  THE  NATURAL  HISTORY  OF  CANCER 

throat,"  and  the  younger  of  cancer  of  the  left  axilla.  Of  his  sisters,  four 
have  died  of  cancer  of  the  breast ;  and  the  two  now  living  are  both 
suffering  from  the  same  disease,  also  of  the  breast. 

9.  There  is  in  the  museum  of  the  Middlesex  Hospital,1  a  specimen  of 
sarcoma  of  the  breast,  removed  from  a  lady  whose  two  sisters  had  similar 

disease also  of  the  breast ;  and  Paget 2  has  cited  the  case  of  a  lady,  the 

victim  of  mammary  scirrhus  (other  members  of  her  family  were  also 
believed  to  have  died  of  "  cancer  "),  whose  three  daughters  all  developed 
adeno-sarcoma  of  the  breast. 


Uterus. 

1.  I  have  known  a  woman,  aged  fifty- three,  with  uterine  cancer, 
whose  maternal  grandmother,  mother  (aged  forty-five),  mother's  sister  ; 
and  the  patient's  two  sisters  (aged  thirty- two  and  thirty-six),  had  all  died 
of  cancer  of  the  uterus.     She  was  one  of  a  family  of  eleven  ;  of  her  other 
brothers  and  sisters  three  died  in  infancy,  and  five  were  still  alive  and 
well. 

2.  Atthill3  mentions  the  case  of  a  woman,  aged  twenty-eight,  with 
uterine  cancer,  whose  mother  and  two  sisters  also  died  of  cancer  of  the 
same  organ. 

3.  Guthmann4  has  met  with  cancer  of  the  corpus  uteri  in  three  sisters  ; 
Veit 6  with  cancer  of  the  cervix  uteri  in  two  sisters  ;   and  Cullen 6  with 
cancer  of  the  uterus  in  three  sisters. 

4.  Paget 7  has  reported  an  instance  of  uterine  cancer  in  grandmother, 
mother  and  daughter. 

5.  Pean  8  met  with  an  instance  of  uterine  sarcoma  in  a  child  two 
years  old,  whose  mother  died — aged  thirty-eight — of  malignant  disease 
of  the  uterus,  her  mother  having  also  died  of  the  same  affection — aged 
thirty-two. 

6.  Woods  Hutchinson  9  refers  to  the  family  history  of  a  lady  medical 
student  whose  grandmother,  mother,  two  maternal  aunts  and  two  sisters, 
all  died  of  cancer — the  uterus  being  the  part  affected  in  four  of  these 
relatives,  and  the  breast  in  two. 


Gastro-Intestinal. 

1.  Of  the  celebrated  Bonaparte  family,  Napoleon  I.,  his  father,  his 
brother  Lucien,  and  two  of  his  sisters  (Pauline  and  Caroline),  all  died  of 
cancer  of  the  stomach. 

1  Pathological  Catalogue,  Nos.  2,079  and  2,093. 

I'  Lectures  on  Surgical  Pathology,"  1854,  vol.  ii.,  p.  260. 
Clinical  Lectures  on  Diseases  of  Women,"  1876,  p.  251. 

'Uber  den  Einfluss  der  Erblichkeit  auf  die  Entstehung  des  Uteruscarcinoms," 
Inaug.  Diss.,  Wiirzburg,  1888. 

"  Veroffentlichungen  des  Comitees  fur  Krebsforschung,"  1902. 
I      Cancer  of  Uterus,"  1901,  p.  648. 
'  Cited  by  Moore,  "  Antecedents  of  Cancer,"  p   16 

'^Tumeurs  de  1'Abdomen,"  1895. 

"  Human  and  Comparative  Pathology,"  1901,  p.  206. 


FAMILY  HISTORY  361 

2.  Twenty-three  families  known  to  Manichon,1  comprised  between 
them  sixty-nine  cancerous  members  ;  and  of  these  the  stomach  was  the 
seat  of  the  disease  in  no  less  than  fifty-seven.     In  the  part  of  the  country 
where  these  families  lived,  consanguineous  marriages  were  frequent. 

3.  A  woman  under  my  observation,  wTith  cancer  of  the  rectum,  had 
lost  a  sister  from  the  same  disease,  which  had  also  caused  the  death  of 
her  mother's  sister,  while  the  patient's  mother  died  of  cancer  of  the 
stomach. 

4.  Hollander  knew  of  a  family  of  which  five  members  had  died  of 
intestinal  cancer  ;  Childe  2  met  with  cancer  of  the  rectum  in  three  sisters  ; 
Korteweg  3  with  cancer  of  the  same  part  in  two  sisters  ;  and,  according  to 
Lebert,  the  celebrated  physician  Broussais  and  his  son,  both  died  of 
rectal  cancer. 

5.  In  Kompe's  4  case,  father  and  son  both  died  of  cancer  of  the  colon  ; 
the  father's  father  died  of  malignant  disease  of  the  cervical  spine ;  the 
mother  died  of  cancer  of  the  uterus,  and  her  mother  of  cancer  of  the 
breast. 

External  Genitalia. 

1.  In  a  man  with  cancer  of  the  penis  known  to  Warren,5  the  father, 
grandfather  and  great-grandfather,  had  all  died  of  the  same  malady  of 
the  same  part. 

2.  Earle6  had  a  patient,   with  epithelioma  of  the  scrotum,  whose 
grandfather,  father  and  brother,  had  all  died  of  the  same  disease. 


Eye. 

1.  The  occurrence  has  been  reported  of  melanotic  sarcoma  of  the 
choioid  of  the  left  eye,  in  mother  and  daughter.  The  mother,  when 
pregnant  with  the  daughter,  who  twenty-one  years  later  developed  the 
same  disease,  was  then  herself  affected  in  the  same  way.  Mother  and 
daughter  had  each  the  diseased  eye  removed  at  the  Royal  London 
Ophthalmic  Hospital,  where  careful  records  were  kept.  Each  tumour 
was  found  to  have  originated  from  precisely  the  same  part  of  the  choroid  ; 
and  the  microscopical  structure  of  each  was  identical — round  and  spindle- 
celled  melanotic  sarcoma. 

In  this  family  it  seems  almost  certain  that  other  of  the  mother's 
relatives  were  similarly  affected,  viz.,  her  father  and  her  twin  sisters, 
each  of  whom  had  lost  an  eye  by  extirpation  for  disease. 

A  report  of  this  case  was  first  published  by  Lawford  and  Collins  ;7  and 
many  years  afterwards  Silcock8  gave  another  account  of  the  same.  As 
there  are  discrepancies  in  the  two  reports,  as  to  the  presumed  nature  of 
the  malady  which  caused  the  mother's  relatives  to  lose  each  an  eye,  the 

These  de  Paris,  1896,  No.  415. 

British  Medical  Journal,  1905,  vol.  ii.,  p.  804. 

Op.  cit.  *  Inaug.  Diss.  Munch.,  1883. 

Cited  by  R.  D.  Gross  in  his  "  System  of  Surgery,"  1882,  vol.  i.,  p.  242. 

Transactions  of  the  Medico-Chirurgical  Society,  London,  vol.  xii.,  p.  305. 

Royal  London  Ophthalmic  Hospital  Reports,  vol.  vii.,  p.  389. 

Transactions  of  the  Pathological  Society,  London,  1892,  vol.  xliii.,  p.  140. 


362  THE  NATURAL  HISTORY  OF  CANCER 

foregoing  account  is  of  the  nature  of  a  compromise,  such  as  seemed  most 
probable  after  careful  study  of  both  of  them. 

2.  An  example  of  malignant  disease  of  the  eyeball,  in  four  brothers 
and  sisters,  is  cited  by  Otto.1 

Glioma. 
Many  remarkable  instances  of  hereditary  glioma  have  been  recorded. 

1.  Thus,  in  Newton's  case,2  of  a  family  of  16  children,  10  had  died 
of  retinal  glioma — the  disease  being  bilateral  in  7  cases.     Of  these  10 
children,  only  1  lived  beyond  the  age  of  three  years,  he  had  been  operated 
on  for  unilateral  glioma,  at  the  age  of   three  years,  and  died,  aged  five 
years,  with  recurrence.     Of  the  affected  children.  5  were  males  and  5 
females.      With  regard  to  the  other  members  of  this  family,   2  died 
shortly  after  birth  of  bronchitis  ;  and  4  were  still  alive  and  well.     One  of 
the  father's  brothers  is  believed  to  have  died  in  infancy,  from  the  same 
malady  ;  but  both  parents  were  alive  and  well. 

2.  H.  Wilson  3  has  seen  eight  children  of  one  family  similarly  affected. 

3.  Other  instances  in  which  several  members  of  the  same  family  have 
been  affected  with  glioma,  have  been  reported  by  Snell,4  Fuchs,  Calderini, 
Graefe,  Sichel  etc. 

4.  Of  the  children  of  two  brothers  known  to  Feinstein,5  three  of  the 
first  family  and  one  of  the  second,  had  succumbed  of  glioma  retinae. 

Miscellaneous  Examples. 

Many  other  examples  of  multiple  hereditary  cancer  may  be  found 
in  the  records  of  medical  science :  I  subscribe  references  of  several 
such,  e.g.,  by  Roper6  (of  a  family  of  7,  6  died  of  cancer — in  females  the 
breast  being  the  part  affected)  ;  Cotoni 7  (6  cases  of  cancer  in  the  same 
family) ;  Warren  8  (6  cases  of  cancer  in  3  generations  of  the  same  family — 
in  all  but  one  the  breast  being  the  part  affected) ;  Striimpell  (2  brothers 
with  sarcoma  of  the  left  kidney)  ;  Hollander  (of  the  31  relatives  and 
descendants  of  a  pair — both  of  whom  died  of  cancer — 16  certainly  died 
of  the  same  disease  and  probably  3  others)  ;  Sprengel  (a  woman  with 
cancer  of  the  breast,  whose  brother,  father  and  2  other  members  of  the 
family,  died  of  cancer  of  the  liver)  etc. 

Cancer  and  other  Tumours  in  Twins. 

Some  years  ago,  Galton  9  published  a  most  instructive  study  of  the  life- 
history  of  twins,  with  the  object  of  determining  the  relative  influence 
between  the  effects  of  tendencies  received  at  birth,  and  those  imposed  by 
the  circumstances  of  their  lives.  He  found  that  many  homologous  twins 

"  Pathological  Anatomy,"  1831,  p.  16  (South's  translation). 

Australian  Medical  Gazette,  May,  1902,  p.  236. 

Transactions  of  the  Pathological  Society,  Dublin,  1871-1874,  p.  108. 

British  Medical  Journal,  1905,  vol.  ii.,  p.  132  ;  also  ibid.,  1904,  vol.  L,  p.  1429. 

Sev.  de*  Sci.  Med.,  1896,  No.  93,  p.  301 

£r»**A  Medical  Journal,  1887.  1  Normandie  Med.,  October  1,  1893. 

Surgical  Observations  on  Tumours,"  p.  281. 
Journal  of  the  Anthropological  Institute,  1876,  vol.  v.,  p.  391. 


FAMILY  HISTORY  363 

suffered  from  identical  maladies,  among  which  were  instances  of  hernia, 
flexures  of  the  digits,  baldness  etc.1  Carbonell  met  with  identical  multiple 
malformations  in  twin  brothers  ;  and  Windle  has  instanced  other  cases 
of  identical  malformations  in  twins.  The  conclusion  Galton  arrived  at,  as 
the  outcome  of  his  investigation  was,  that  nature  was  far  stronger  than 
nurture  :  "  We  are  too  apt  to  look  upon  illness  and  death  as  capricious 
events,  whereas  the  fact  of  the  maladies  of  two  twins  being  continually 
alike,  shows  that  illness  and  death  are  necessary  incidents  in  a  regular 
series  of  constitutional  changes  beginning  at  birth,  upon  which  external 
circumstances  have,  on  the  whole,  very  small  effect." 

No  examples  of  tumour  are  comprised  among  Galton' s  cases  ;  but, 
since  then,  several  instances  of  this  kind  have  been  described. 

Of  these,  one  of  the  most  remarkable,  is  the  Lawford-Collins-Silcock 
case,  in  which  twin  sisters  each  had  the  left  eye  removed  for  pigmented 
sarcoma  of  the  choroid,  as  previously  described ;  and  other  instances 
of  "  cancer  "  in  twins  have  been  recorded  by  Bautista  Claveria,  Gaylord 
and  Wilder. 

Peacock  has  seen  Hodgkin's  disease  in  twin  boys,  four  years  old  ; 
Anseaux  identical  goitrous  tumours  in  twin  brothers  ;  Ahlfeld,  congenital 
hydrocele,  on  the  right  side,  in  male  twins ;  and  Leared,  ovarian 
cystoma  in  twin  sisters.  Conner  met  with  pigment  staining — which  is 
often  a  pre-cancerous  lesion — of  the  lip  and  mouth,  in  twins. 

These  cases  alone  suffice  to  show,  that  there  is  an  inherited  element  in 
cancer  and  tumour  growth. 

In  Animals. 

Some  remarkable  examples  of  the  hereditary  transmission  of  melanosis 
in  horses  are  cited  by  Virchow.2  One  of  these,  a  young  white  stallion,  with 
melanosis  of  the  anus,  transmitted  this  disease  to  all  its  white  descendants, 
whereas  those  of  a  darker  colour  escaped.  From  horses  thus  bred,  the 
disease  became  widely  diffused  throughout  the  neighbouring  country. 

This  is  the  only  instance  of  the  kind  I  have  met  with  in  the  animal 
world  ;  but,  when  attention  is  specially  directed  to  this  subject,  no  doubt 
others  will  be  forthcoming. 

Heredity  of  Non-malignant  Tumours. 

Here  it  may  be  mentioned,  that  similar  examples  of  multiple  heredity 
occur  also,  in  those  subject  to  various  non-malignant  tumours. 

Thus,  Beyea  3  met  with  uterine  myomata  in  four  sisters,  whose  mother, 
aunt  and  grandmother  had  all  been  affected  in  the  same  way  ;  and,  a 
family  of  nine  sisters,  furnished  Lawrie  4  with  five  instances  of  uterine 
myomatous  disease,  and  five  of  cataract — three  of  the  myomatous  sisters 
having  also  the  latter  affection.  Doran  and  Engestrom  have  also  each 
found  uterine  myomata  in  three  sisters. 

1  Siebold  has  seen  twins  with  six  digits  on  each  hand  and  foot];  "andJDelbarre  twins, 
each  with  a  supernumerary  right  thumb: 

2  "Path,  des  Tumeurs,"  t.  ii.,  p.  236. 

3  American  Journal  of  Obstetrics,  etc.,  vol.  xliii.,  p.  703. 

4  British  Medical  Journal,  1904,  vol.  i.,  p.  357. 


364  THE  NATURAL  HISTORY  OF  CANCER 

An  instance  of  ovarian  cystoma  in  five  sisters,  has  been  reported  by 
Keith  j1  similar  disease  in  a  mother  and  her  two  daughters,  by  Simpson  ;2 
while  Lohlein  3  met  with  bilateral  ovarian  cystoma,  in  three  sisters  ;  and 
Hue  4  with  bilateral  ovarian  dermoids,  in  two  sisters. 

Broca  5  knew  a  lady  and  her  three  daughters,  who  had  fibro-adenoma 
of  the  breast. 

Multiple  adenoid  polypi  of  the  rectum  were  found  by  T.  Smith,  in 
three  members  of  a  family  of  six  ;  and  in  Child's  previously  cited  case  of 
cancer  of  the  rectum  in  three  sisters,  two  were  affected  also  with  multiple 
polypi  of  the  part. 

Multiple  exostoses  often  manifest  the  same  peculiarity  in  a  marked 
degree  :  thus,  in  an  instance  recorded  by  Reclus,  a  man  and  his  three  sons 
were  all  affected  in  this  way,  as  also  was  his  sister,  her  daughter,  four 
children  of  the  latter,  and  seven  grandchildren.  In  a  similar  case  recorded 
by  Teissin,  three  children  of  one  family  were  thus  affected,  as  well  as  their 
father  and  paternal  grandfather.  Here  there  was  inheritance  in  the 
direct  line,  in  three  successive  generations. 

An  interesting  example  of  hereditary  multiple  angiomata  of  the  skin 
and  mucous  membranes,  in  a  mother,  her  three  sons  and  one  daughter, 
has  lately  been  recorded  by  F.  P.  Weber,  who  cites  similar  cases  by  Osier 
and  Kelly. 

In  like  manner,  Nicolle  and  Halipre  have  met  with  thirty-six  cases  in 
six  generations,  of  a  peculiar  dystrophy  of  the  hair  and  nails. 

These  examples  suffice  to  make  clear  the  similarity  between  malignant 
and  non-malignant  tumours,  in  respect  to  this  form  of  heredity. 

Homotopic  Transmission. 

A  remarkable  feature  about  many  cases  of  inherited  cancer  and  other 
tumours  is  that  the  disease,  like  normal  structure,  is  homotopic  in  its 
transmission ;  that  is,  it  attacks  the  corresponding  organ  in  each  of  the 
related  individuals.  This  is  especially  noticeable  in  Sibley's  case,  where 
the  mother  and  her  five  daughters  all  had  cancer  of  the  left  breast ;  in 
Guthmann's  case  of  cancer  of  the  corpus  uteri  in  three  sisters ;  in  Silcock's 
case  of  melanotic  sarcoma  of  the  choroid  of  the  left  eye  in  three  genera- 
tions ;  in  the  Bonaparte  family,  where  the  stomach  was  the  part  affected 
in  every  instance  ;  in  Warren's  case  of  cancer  of  the  penis  in  four  genera- 
tions etc. 

Although  this  form  of  transmission  often  defaults,  it  is  nevertheless 
noteworthy  that,  on  the  average — taking  all  the  seats  of  inherited  cancer 
into  consideration — homotopic  transmission  preponderates. 

Thus,  of  the  48  seats  of  inherited  cancer,  in  my  analysis  of  the  family 
history  of  136  cases  of  mammary  cancer  in  women,  the  breast  was  the 
organ  affected  in  19  ;  similarly  of  the  15  seats  of  the  disease  inherited  from 
Madame  Z.,  who  had  mammary  cancer,  in  9  the  breast  was  affected  ;  and 
of  the  32  seats  of  hereditary  disease,  noted  in  my  analysis  of  the  family 
history  of  142  uterine-cancer  cases,  in  13  the  uterus  was  the  part  affected. 

*  British  Medical  Journal,  1878,  vol.  ii.,  p.  593. 

"•  Lancet,  1905,  vol.  i.,  p.  799.  3  Monatschr.  f.  Geb.  u.  Gyn.,  February,  1896. 

La  Jiev.  Med.  de  Aormandie,  July  25, 1904.         6  '•  Trait£  des  Tumours,"  t.  i.,  p.  156. 


FAMILY  HISTORY 


365 


The  tendency  to  homotopic  transmission  may  thus  be  taken  as  the 
established  rule,  although  the  number  of  cases  in  which  heterotopic 
transmission  occurs  is  by  no  means  inconsiderable.  I  can  discover  no 
ground  for  the  dictum,  that  homotopic  transmission  is  especially  apt  to 
prevail  among  near  relatives,  and  heterotopic  transmission  among 
distant  ones. 

From  the  foregoing  facts,  it  may  be  inferred  that  the  molecular  proto- 
plasmic disturbance,  which  eventuates  in  inherited  malignant  disease, 
affects  the  whole  of  the  epithelial  or  connective-tissue  elements  of  the 
body,  as  the  case  may  be  ;  but  that  its  influence  is  most  potent  in  that 
part,  which  corresponds  to  the  dominant  seat  of  the  disease  in  affected 
relatives.  Such  indications  point  to  intrinsic  rather  than  to  extrinsic, 
causative  conditions. 

Family  History  Analyses. 

In  further  illustration  of  this  subject,  I  append  analyses  of  the  family 
history  of  a  series  of  mammary  and  uterine  cancer  patients,  so  as  to  show 
the  relations  affected  and  the  seats  of  the  disease. 

The  family  histories  of  136  women  with  mammary  cancer,  yielded  on 
analysis  the  following  particulars  : 

Father's  father  (in  two  families) 


Father's  mother  (in  two  families) 

First  cousin  of  father's  mother  (in  one  family) 

Father  (in  five  families)          


Father's  sister  (in  ten  families) 

Father's  mother  (in  three  families) 
Sister  of  mother's  father  (in  one  family) 

Mother  (in  seven  families) 

Mother's  sister  (in  six  families) 

Mother's  brother  (in  one  family) 

Female  cousin  on  mother's  side  (in  two  families) 

Patient's  sister  (in  five  families) 

Patient's  brother  (in  two  families) 
Patient's  daughter  (one  family) 


fNoae. 

X  CEsophagus. 

/Breast. 

\Breast. 

(Esophagus. 
/"Breast. 

Lip. 
\  Hand. 

Internal. 
^Liver. 

Breast  (5). 

Mouth. 

Face. 
}  Scalp. 

Liver. 
I  Internal. 

{Breast. 
Uterus. 
Locality  not  stated. 

Breast. 

Uterus  (2). 

Stomach. 

Breast. 

Tongue. 

Internal  (2). 

Breast  (4). 

Internal. 

Tongue. 

Groin, 
f  Breast. 
\Locality  not  stated. 

(Breast  (3). 
Uterus. 
Locality  not  stated. 
/Throat. 
\Back. 
Internal. 


366  THE  NATURAL  HISTORY  OF  CANCER 

In  eight  of  these  families  the  disease  had  involved  more  than  a  single 
member :  in  one  family  seven  members  were  affected,  in  another  four,  and 
in  six  families  three  members  were  attacked.  The  disease  prevailed  in  the 
families  of  both  parents,  in  four  instances. 

The  above  48  seats  of  hereditary  disease  may  be  grouped  thus: 
breast  19,  internal  6,  uterus  4,  liver  2,  oesophagus  2,  aU  others  15. 

The  recoids  of  the  family  history  of  142  consecutive  uterine  cancer 
patients,  yielded  the  following  results  : 

Father's  brother  (in  one  family) Face- 

(Stomach  (brother). 

I  Breast  (female  cousin). 
Father's  brother  and  three  cousins  (in  one  family)  . .  -j  >jeck  (maje  COUsin). 

vFoot  (male  cousin). 

I  Uterus. 
Father's  sister  (in  three  families)      ..         ..          •-          ••   ]  Intestine. 

I^Arm. 

Maternal  grandmother  (in  one  family)  ..         ..         ••      Uterus. 

/Uterus  (2). 

I  Breast  (2). 

i  Stomach  (2). 

Mother  (in  nine  families)        j  intestine. 

Abdomen. 


Mother's  brother,  and  child  of  mother's  sister  (in  four 
families) 


(Uterus  (2). 

Mother's  sister  (hi  six  families)         \  Breast  (2). 

(Locality  not  stated  (2). 

Stomach  (brother). 
Face  (brother). 
Locality  not  stated 

(brother). 
Stomach  (sister's  child). 


Patient's  sister  (in  eight  families)      ..          ..          ..          ..   \Breast  (2 

Patient's  brother  (in  one  family)      . .          . .          . .          . .      Stomach. 

Patient's  daughter  (hi  one  family)     . .          . .       •  . .         . .      Uterus. 

These  38  seats  of  hereditary  disease  may  be  grouped  thus  :  uterus  13, 
breast  7,  stomach  6,  face  3,  locality  not  stated  3,  intestine  2,  abdomen, 
arm  and  foot,  each  1. 

In  two  of  these  families  more  than  a  single  relative  was  affected  :  in 
one  of  them  all  the  affected  relatives  were  on  the  mother's  side,  and  in 
the  other  all  were  on  the  father's  side. 


General  Conclusions  as  to  Cancer  Inheritance. 

In  order  to  ascertain  the  frequency  of  cancer  inheritance,  I  have  made 
an  analysis  of  the  records  of  the  family  history  of  numerous  cancer 
patients  with  the  following  results  : 

Of  142  cases  of  uterine  cancer,  there  was  history  of  heredity  in  28 
(19-7  per  cent.). 

Of  136  cases  of  mammary  cancer,  there  was  history  of  heredity  in  33 
(24-2  per  cent.). 


FAMILY  HISTORY  367 

Of  92  other  female  cancer  cases,  there  was  history  of  heredity  in  22 
(23-9  per  cent.).  yxs 

Thus,  of  these  370  female  cancer  patients,  there  was  history  of  heredity  A 
in  83  (22-4  per  cent.). 

Of  209  men  suffering  from  cancer,  there  was  history  of  cancer  heredity 
in  only  23  (11  per  cent.).     I  attribute  this  difference  to  the  fact,  that  the    v 
men  knew  so  much  less  than  the  women,  of  the  details  of  their  family 
history. 

From  whatever  point  of  view  the  subject  is  regarded,  these  foregoing 
are  very  high  percentages.  Many  anomalies  well  known  to  be  hereditary, 
yield  on  inquiry  a  much  lower  proportion  ;  for  instance,  of  92  cases  of 
supernumerary  mammary  structures  analysed  by  Leich  tens  tern,  there 
was  history  of  heredity  in  only  7,  or  in  7-6  per  cent.  In  my  opinion, 
data  such  as  the  above,  are  of  themselves  presumptive  evidence  of  the 
hereditability  of  cancer  ;  for,  it  is  certain,  that  no  such  great  proportion  > 
of  cancerous  relatives  is  to  be  found,  among  the  relatives  of  the  non- 
cancerous. 

Thus,  of  101  women  with  non-malignant  tumours,  there  was  history 
of  cancer  in  only  16  families  (15-8  per  cent.).  The  above  data  were  col- 
lected by  myself,  and  the  inquiries  were  made  with  equal  care  in  both 
sets  of  cases. 

The  proportion  of  women  with  cancer  of  the  breast,  among  whose 
relatives  there  was  a  history  of  cancer,  has  been  estimated  by  Butlin  at 
about  37  per  cent.,  by  Nunn  at  29-3  per  cent.,  by  myself  at  24-2  per  cent., 
and  by  Leaf  at  23  per  cent.  ;  whenever  inquiries  of  this  kind  are  made, 
in  a  careful  and  systematic  manner,  the  proportion  of  relatives  affected 
will  always  be  found  to  vary  within  these  limits  or  in  close  approximation 
thereto. 

When  therefore  an  inquiry  was  lately  made  at  the  Middlesex  Hospital,1 
as  to  the  influence  of  heredity  in  cancer,  it  is  surprising  to  find  that  the 
basis  on  which  Karl  Pearson  was  invited  to  exercise  his  well-known 
biometrical  skill  was  ;  that  the  proportion  of  cancerous  relatives  amounted 
only  to  8-56  per  cent.,  of  1,000  female  cancer  patients  interrogated. 

With  regard  to  this  result,  I  am  able  to  state  positively  of  my  own 
knowledge,  that  inquiries  yielding  such  a  low  percentage  of  heredity, 
must  necessarily  have  been  carried  out  in  a  careless  and  perfunctory 
manner  ;  and,  consequently,  conclusions  resting  on  such  a  basis  are 
destitute  of  any  scientific  validity.  When,  therefore,  it  is  claimed  that 
this  inquiry  has  proved  that  cancer  is  not  a  hereditable  disease,  it  will 
be  well  to  recollect  the  worthless  nature  of  the  substratum,  on  which  this 
conclusion  is  based.  This  Middlesex  hospital  fiasco  ought  to  become 
memorable,  as  a  warning  example  of  the  pitfalls  likely  to  overtake  those 
who  indulge  in  biometrical  flights,  without  having  made  adequate  ante- 
cedent survey  of  the  actual  field  of  operations.  In  a  matter  of  this  sort 
we  must  remember  that  error  does  not  become  truth,  because  it  is  repeated 
thousands  of  times  by  thousands  of  persons. 

From  the  foregoing  facts  it  may  be  gathered,  that  the  transmission  of 

1  Archives  of  the  Middlesex  #ospifaZ,«l904,  vol.  ii.,  pp.  104  and  127;  also  ibid.,  vol.  v., 
p.  103. 


368  THE  NATURAL  HISTORY  OF  CANCER 

malignant  and  other  tumours  by  inheritance,  takes  place  in  accordance 
with  the  same  general  laws  that  govern  physiological  heredity  ;  but, 
whereas,  under  physiological  conditions,  "  the  inheritance  of  any  character 
whatever  is  the  rule,  and  non-inheritance  the  anomaly,"  under  patho- 
logical conditions— which  imply  failure  or  undoing  of  evolution — 
the  tendency  is  just  the  converse  :  hence,  with  favourable  circumstances, 
morbid  states  of  this  kind  tend  to  die  out  in  the  course  of  transmission 
(vis  medicatrix  natures).  In  this  consideration,  there  is  assurance  of  the 
feasibility  of  prevention. 

In  accordance  with  these  indications,  I  find  that  the  tendency  to 
cancer  may  be  transmitted  directly  or  through  parents  ;  indirectly  or 
through  collaterals ;  and  by  reversion  (atavism),  after  skipping  one  or 
more  generations.  Examples  of  single-family  prevalence,  such  as  I  have 
cited  in  the  early  part  of  this  chapter,  may  probably  be  included  under 
the  last  heading. 

In  the  foregoing  analyses,  there  wras  history  of  the  transmission  of 
cancer  directly  from  parents,  in  about  8  per  cent,  of  the  total  cases. 

It  rarely  happens  that  both  parents  are  cancerous  ;  but,  such  an 
unfortunate  combination,  undoubtedly  increases  the  proclivity  to  morbid 
inheritance. 

Thus,  of  136  family  histories  of  breast-cancer  patients  investigated  by 
me,  in  only  2  instances  were  both  parents  cancerous.  These  marriages 
produced  7  children,  of  whom  2  had  died  of  cancer,  or  1  in  3-5.  Seven 
marriages,  in  which  only  one  parent  was  cancerous,  produced  62  children, 
of  whom  10,  or  1  in  6-2  had  become  cancerous.  Six  marriages,  in  which 
although  neither  parent  was  cancerous,  the  disease  existed  in  their 
collaterals,  produced  41  children,  of  whom  8,  or  1  in  5-1  had  become 
cancerous. 

In  spite  of  the  numerical  inadequacy  of  these  data,  I  think  this  analysis 
gives  fairly  correct  indications. 

The  phenomena  of  inheritance  teach  us,  that  the  actual  product  of  a 
fertilized  germ  never  represents  the  full  measure  of  its  potentiality.  Only 
a  portion  of  the  many  varying  tendencies  inherited  by  the  reproductive 
cells,  from  their  long  line  of  ancestors,  are  actually  evolved  in  each 
generation.  Hence,  in  normal  heredity,  we  constantly  see  transmitted, 
besides  developed  structures,  certain  tendencies  and  predispositions. 

Thus,  the  male  and  female  secondary  sexual  characters  are  trans- 
mitted through  each  sex,  though  usually  developed  in  one  alone. 
Similarly,  tendencies  are  transmitted  through  the  earlier  years  of  life, 
that  are  only  subsequently  developed.  In  like  manner,  we  often  see 
qualities  transmitted  in  a  latent  state  through  one  or  more  generations, 
and  then  suddenly  developed,  as  in  the  wonderful  phenomena  included 
under  the  term  "  reversion."  By  virtue  of  these  considerations,  it  has  been 
truly  said,  that  to  know  a  man  well,  we  must  know  his  relations — grand- 
parents, parents,  uncles,  aunts,  cousins,  brothers,  sisters,  children — in 
them  we  shall  often  see  developed  his  own  latent  tendencies.  For  this 
reason,  those  who  neglect  collaterals  in  studying  heredity,  are  greatly  in 
error. 

It  not  infrequently  happens  that  such  latent  tendency  to  disease  in 


FAMILY  HISTORY  369 

ancestors,  although  it  never  becomes  effective  in  them,  nevertheless  does 
so  in  their  descendants.  Thus,  cases  occur  in  which  cancerous  grand- 
parents transmit  the  disease  to  their  grandchildren,  while  their  own 
offspring  escape  (atavism),  as  of  our  own  royal  family. 

This  happened  in  seven  of  the  136  cases  of  cancer  of  the  female  breast 
analysed  by  me,  or  in  5-1  per  cent.  In  three  of  these  cases,  the  disease 
was  inherited  from  the  maternal  grandmother,  in  two  from  the  paternal 
grandmother,  and  in  two  from  the  paternal  grandfather.  In  three  cases, 
the  locality  affected  in  the  grandparents,  as  in  the  grandchildren,  was  the 
breast ;  in  the  other  four  cases,  the  localization  of  the  disease  in  the 
grandparents,  differed  from  that  in  the  grandchildren.  Whether  cancer 
is  ever  transmitted  by  reversion,  after  skipping  more  than  a  single 
generation — as  often  happens  in  physiological  heredity — I  am  unable  to 
state,  and  I  know  of  no  facts  bearing  directly  on  this  point ;  but,  on  a  priori 
grounds,  it  seems  probable  ;  and  this  may  be  the  explanation  of  such 
remarkable  examples  of  single-family  prevalence,  as  I  have  instanced  in 
the  early  part  of  this  chapter. 

Much  commoner  than  true  atavism,  or  than  heredity  by  direct  descent 
from  parents,  is  a  form  of  inheritance  in  which  the  disease  is  transmitted 
through  parents  etc.,  who  themselves  never  manifest  it,  although  their 
sisters,  brothers  or  other  relatives  do.  On  reference  to  my  analysis  of 
mammary-cancer  cases,  it  will  be  seen  that  the  inherited  disease  mani- 
fested itself,  in  this  way,  in  the  father's  sisters  in  ten  families,  the  breast 
being  the  organ  affected  in  five  ;  and  in  six  families  in  the  mother's  sisters, 
the  breast  being  affected  in  four. 

It  will  generally  be  found  that  the  birth  of  the  subjects  of  direct  cancer 
heredity,  dates  from  a  period  long  anterior  to  that  at  which  the  disease 
appeared  in  their  parents.  Thus,  in  Broca's  case,  the  four  daughters  of 
Madame  Z.,  who  all  died  cancerous,  were  born  fifteen,  twenty-five,  twenty- 
six  and  thirty  years  respectively,  before  the  period  when  their  mother 
died  of  the  disease — that  which  was  then  latent  in  the  parent  was  trans- 
mitted potentially  to  the  offspring. 

It  is  a  legitimate  inference  from  what  has  been  stated,  that  the  special 
tendency  to  cancer  is  of  gradual  evolution ;  and  that,  without  this  ante- 
cedent preparation,  the  disease  can  seldom  be  developed  under  ordinary 
circumstances. 

Inherited  cancer  manifests  itself  much  more  frequently  in  the  female, 
than  in  the  male  relatives,  although  the  disease  is  as  often  derived  from  \ 
the  father's  as  from  the  mother's  side  of  the  family.  My  analyses  show 
this  very  well.  Thus,  of  47  affected  relatives  in  the  mammary-cancer 
series,  there  were  10  males  to  37  females ;  and  of  38  relatives  in  the 
uterine-cancer  series,  8  were  males  and  30  females. 

In  cases  of  multiple  family  cancer,  this  tendency  of  the  inherited 
disease  to  repeat  itself  unduly  in  the  female  sex  is  especially  noticeable. 
Thus,  in  Broca's  case,  all  the  persons  attacked  but  one,  were  females.  Of 
the  19  daughters  and  granddaughters  of  Madame  Z.,  who  attained  the 
age  of  thirty,  14  became  cancerous  ;  but  of  7  males  only  1  was  thus 
affected. 

As  in  normal  heredity — but  with  less  constancy — cancer  tends  to 

24 


370  THE  NATURAL  HISTORY  OF  CANCER 

appear  in  the  offspring,  at  about  the  same  age  that  it  appeared  in  the 
ancestor.  Hence,  like  gout,  cataract,  insanity,  and  some  other  herit- 
able conditions,  the  disease  usually  does  not  manifest  itself  until  an 
advanced  period  of  post-natal  life. 

It  has  been  suggested  that :  "  The  nearer  to  the  cancer  age,  in  a 
parent,  a  child  is  begotten,  the  greater  is  the  probability  that  a  tissue 
proclivity  to  cancer  will  be  inherited."  I  have  been  unable  to  find 
any  evidence  in  support  of  this  dictum  ;  but  I  know  of  several  circum- 
stances that  seem  to  negative  it.  As  I  have  previously  indicated,  the 
subjects  of  uterine  and  mammary  cancer  whose  life-history  I  have 
studied,  married  earlier  and  had  more  children  than  the  generality  of 
women ;  and,  if  we  study  the  national  statistics  relating  to  the  propor- 
tion of  minors  married  and  the  age  at  marriage,  during  the  last  half- 
century,  it  will  be  found — although  there  have  been  very  marked  fluctua- 
tions in  these  respects — that  no  corresponding  alterations  have  ensued 
in  the  incidence  of  the  constantly  increasing  cancer  mortality.1 

It  has  also  been  suggested,  that  during  the  course  of  its  transmission 
by  inheritance,  the  tendency  of  malignant  disease  may  be  transmuted 
into  some  form  of  non-malignant  tumour  disease.  On  a  priori  grounds, 
I  have  no  objection  to  offer  to  this  suggestion ;  but  the  facts  collected 
by  me  show,  that  the  existence  of  such  a  coincidence  in  the  family  history 
of  cancer  patients,  is  most  exceptional.  Thus,  the  family  history  of 
345  female  cancer  patients,  gave  evidence  of  non-malignant  tumours 
only  in  13  instances,  or  3-7  per  cent. 

With  regard  to  the  influence  of  consanguinity,  inquiries  were  made  of 
thirty-three  women  with  mammary  cancer,  two  of  whose  parents  were 
blood  relations. 

In  one  of  these  families,  the  parents  being  first  cousins,  the  father 
died  of  heart  disease,  aged  sixty-six,  his  father  having  died  insane  ;  the 
mother  died,  aged  seventy-eight,  of  dropsy  :  there  were  five  children 
of  the  marriage,  of  whom  two  died  in  infancy,  and  two  sisters  were  alive 
and  well ;  there  was  no  history  of  cancer,  tumour  or  phthisis  in  this 
family. 

In  the  other  case,  the  parents  were  third  or  fourth  cousins,  the  father 
died,  aged  fifty-five,  of  phthisis,  his  mother  having  died  of  cancer  of 
the  breast ;  the  mother  died  aged  eighty,  of  old  age. 

Similar  inquiries  were  made  of  fifty-five  uterine-cancer  patients,  but 
in  only  one  instance  were  the  parents  blood  relations. 

In  this  family,  they  were  first  cousins,  and  both  parents  were  still 
alive  and  well — the  father  aged  seventy-five,  the  mother  aged  seventy ; 
their  offspring  comprised  ten  children,  and  there  was  no  history  of 
cancer,  phthisis,  or  insanity  in  the  family. 

Hereditary  Proclivities  Correlated  with  Cancer. 

Study  of  the  family  history  of  a  large  number  of  cancer  patients 
shows,  that  certain  hereditary  proclivities  predominate  among  the 
relatives,  as  follows  : 

1   Vide  Chapter  XVI. 


FAMILY  HISTORY  371 

1.  In  the  preceding  chapter,  I  had  occasion  to  set  forth  the  various 
inter-relations  of  cancer  and  tubercle,  as  indicated  by  the  life-history  of 
cancer  patients  ;  it  now  remains  for  me  to  point  out  the  inter-relations 
of  these  maladies,  as  revealed  by  study  of  the  family  history. 

In  this  connexion,  the  first  fact  to  attract  attention  is,  that  pulmonary 
tubercle  is  by  far  the  most  prevalent  disease  among  the  relatives  of  can- 
cerous persons.  Such  a  result  is  only  what  might  have  been  expected 
a  priori,  considering  the  frequency  of  tuberculous  disease  in  the  com- 
munity at  large ;  but,  a  great  mistake  has  been  made  in  taking  it  for 
granted,  on  this  account,  that  the  relatives  of  cancerous  persons  have 
no  special  proclivity  to  tubercle.  On  the  contrary,  as  I  shall  proceed 
to  show,  such  persons  are  very  much  more  prone  to  it  than  the  rest  of 
the  community ;  indeed,  their  liability  to  phthisis  is  so  considerable,  as 
even  to  equal  that  of  the  phthisical  themselves. 

No  statistics  show  a  greater  amount  of  heredity  in  phthisis  than 
Dr.  R.  Thompson's,1  because  he  has  included  in  his  list  only  those  cases 
in  which  the  family  history  had  been  very  completely  recorded.  He 
obtained  history  of  heredity  in  44  per  cent,  of  5,000  consecutive  phthisical 
cases — 58  per  cent,  in  females,  and  36  per  cent,  in  males.  Now,  my 
analysis  of  the  family  history  of  134  women  with  mammary  cancer, 
shows  a  history  of  phthisis  in  55  per  cent.,  which  is  almost  as  high  a 
proportion  as  Thompson's  ;  similarly,  of  129  uterine-cancer  patients, 
there  was  family  history  of  phthisis  in  60,  or  in  46-5  per  cent. 

The  amount  of  hereditary  phthisis  among  the  rest  of  the  community, 
is  certainly  very  much  less  than  this  ;  it  has  been  estimated  by  Dovey,2 
from  analysis  of  the  family  history  of  409  non-consumptive  life-policy 
holders,  at  10-8  per  cent.  Kuthy's 3  analysis  of  the  family  history  of 
108  non-tuberculous  persons,  gives  a  history  of  tubercle  in  28-5  per 
cent.,  which  is  the  highest  estimate  I  know  of.  Nothing,  therefore, 
can  be  plainer,  than  that  the  relatives  of  cancerous  patients  are  very 
much  more  prone  to  tubercle,  than  the  rest  of  the  community.  This 
is  borne  out,  by  the  results  deducible  from  my  analysis  of  the  causes  of 
death  of  the  brothers  and  sisters  of  patients  with  mammary  cancer,  in 
88  families.  These  families  averaged  8-8  members  each,  in  all  774  indi- 
viduals. Now,  one  or  more  deaths  from  phthisis  took  place  in  40  of  these 
families.  Supposing  only  a  single  death  to  have  occurred  in  each  of  them, 
this  would  be  equivalent  to  1  death  from  phthisis  in  19  members  ;  whereas, 
the  mortality  from  phthisis  in  the  general  population  in  1885,  amounted 
only  to  1  in  570.  Similarly,  among  83  fathers  of  mammary-cancer 
patients,  who  had  died  of  various  causes,  the  mortality  from  phthisis 
was  22,  or  1  in  38  ;  among  71  mothers  it  was  18,  or  1  in  39  ;  thus,  among 
these  154  parents,  it  was  40,  or  1  in  3-8  ;  whereas,  the  ratio  of  deaths 
from  phthisis  to  the  total  mortality  in  the  general  community,  in  1885, 
amounted  only  to  1  in  11.  Analyses  of  the  family  history  of  other  forms 
of  cancer,  yield  similar  results. 

Long  study  of  the  family  history  of  cancer  patients  has  convinced 
me,  that  most  of  the  latter  are  the  surviving  members  of  tuberculous 

1  "Family  Phthisis,"  London,  1885.  3  Cited  by  Thompson  (op.  cit.,  p.  16). 

3  Put.  Med.  Chir.  Presse,  1894,  No.  51. 

24—2 


372  THE  NATURAL  HISTORY  OF  CANCER 

families;  and  the  facts  just  cited  confirm  this  belief.  Hence,  I  con- 
clude that  no  hereditable  condition  is  more  favourable  to  the  develop- 
ment of  cancer,  than  that  which  gives  proclivity  to  tubercle. 

Another  consideration  which  accords  Avith  the  foregoing  is,  that  in 
families  where  cancer  prevails  —  according  to  Moore  —  the  elder  members 
are  more  prone  to  become  cancerous  than  the  younger  ones,  the  first- 
born being  the  most  liable  ;  whereas,  with  regard  to  phthisis,  it  has  been 
shown  by  Thompson,  that  the  younger  members  are  the  more  liable  — 
the  greatest  liability  being  with  the  last  born. 

According  to  Virchow,1  predisposition  to  tubercle  is  always  con- 
comitant with  special  proclivity  to  inflammations.  Ricochon2  has 
shown,  that  congenital  malformations  occur  with  undue  frequency  in 
tuberculous  families  ;  and  Critzmann  found  that  a  tendency  to  malforma- 
tions and  cancer  occurred  alternately  in  certain  families. 

2.  If  similar  investigations  were  set  on  foot  with  regard  to  other 
diseases,  I  believe  it  would  be  found  that  the  tuberculous  predisposition 
y  gives  proclivity  to  many  of  them,  as,  for  instance,  it  certainly  does  to 
insanity.  Thus,  Clouston  3  found  tuberculous  deposits  twice  as  often  in 
the  bodies  of  those  who  died  insane,  as  in  the  bodies  of  those  who  died 
sane  ;  and  he  has  proved,  that  hereditary  predisposition  to  insanity  is 
much  greater  among  the  tuberculous,  than  among  the  non-tuberculous. 
In  this  connexion  it  is  worthy  of  note,  that  the  relatives  of  cancerous 
persons  are  more  prone  to  insanity,  than  are  the  relatives  of  the  non- 
cancerous  ;  at  least,  this  is  the  conclusion  I  draw  from  the  fact,  that 
51  female  cancer  patients  under  my  observation  gave  a  family  history 
of  insanity  in  7  cases,  or  in  13-7  per  cent.  ;  whereas,  29  women  with 
non-malignant  neoplasms,  knew  of  insane  relatives  only  in  3  instances, 
or  in  10-4  per  cent.  ;  and  the  latter  is  probably  a  higher  percentage  than 
would  be  met  with  in  the  general  community. 

In  his  special  Report  on  cancer  in  Ireland,  the  Registrar-General 
remarks  :4  "In  a  large  number  of  instances  where  members  of  a 
family  are  afflicted  ^with  cancer,  other  members  suffer  from  lunacy, 
idioc  etc.  J'VNAJ  *"*•  **o 


^ 
idiocy  etc.    J'VNAJ  *"*•  P4 

Ricochon5  also  found  indications  of  a  certain  relationship  between 
tubercle,  neuropathies  and  cancer:  thus,  53  individuals  affected  with 
phthisis,  had  181  tuberculous,  83  neuropathic,  and  28  cancerous  relatives. 

In  the  preceding  chapter,  I  showed  that  the  liability  of  insane  persons 
to  become  cancerous,  is  decidedly  below  the  average. 

From  the  foregoing  considerations,  it  appears  as  if  predisposition  to 
insanity,  like  predisposition  to  tubercle—  with  which  indeed  it  is  often 
allied—  gives  proclivity  to  cancer,  although  developed  insanity—  like 
active  tuberculous  disease—  seldom  coexists  with  cancerous  lesions. 

3.  Many  authors  regard  apoplexy  as  a  manifestation  of  the  same 
disposition,  of  which  insanity  is  also  an  outcome;  and  my  analysis 
hows  that  this  disease  is  unduly  prevalent  among  the  relatives  of 

"Pathologic  des  Tumeurs,"  1871,  t.  iii.,  p.  164 

Rev.  de  la  Tuberculose,  t.  i.,  p  11 

Cited  by  Maudsley,  "  Pathology  of  Mind,"  p.  112. 

OBca1       '  Thirty'second  Annual  Report  of  the  Registrar  -General  of  Ireland. 


L        FAMILY  HISTORY  373 

cancerous  persons.  *^  Thus,  of  154  parents  of  women  with  mammary 
cancer,  who  died  of  various  causes,  17  died  of  apoplexy,  or  1  in  9  ; 
whereas,  the  ratio  of  deaths  from  apoplexy  to  the  total  mortality  of  the 
general  population  in  1884,  was  only  1  in  36.  Similar  undue  frequency 
of  this  disease,  is  noticeable  among  the  brothers  and  sisters  of  these 
cancer  patients  ;  for,  while  1  in  258  of  the  latter  died  of  apoplexy,  the 
mortality  from  it  in  the  general  community  amounted,  in  1884,  only  to 
I  in  1,841. 

4.  As  mentioned  in  the  preceding  chapter,  the  members  of  cancer 
families  have  an  undue  proclivity  to  arthritic  manifestations. 

5.  There  still  remain  to  be  considered  two  other  proclivities,  to  which 
the  members  of  cancer  families  are  remarkably  subject,  viz.,  longevity 
and  great  reproductive  fecundity.  v 

The  evidence  furnished  by  my  analyses  as  to  the  longevity  of  the 
parents  of  cancer  patients,  is  of  the  most  striking  and  conclusive  kind. 
To  prove  this  it  will  suffice  to  mention  only  a  few  of  the  leading  facts, 
derived  from  the  mammary-cancer  analysis. 

Of  112  dead  fathers  14  attained  the  age  of  eighty,  which  is  equivalent 
to  1,250  per  10,000  ;  whereas,  in  the  general  population,  only  463  males 
live  to  this  age  out  of  10,000. 

Of  103  dead  mothers  17  attained  the  age  of  eighty,  which  is  equivalent 
to  1,650  per  10,000  ;  whereas,  in  the  general  population,  only  682  females 
live  to  this  age  out  of  10,000. 

Of  these  215  dead  parents  2  attained  the  age  of  ninety-five,  which  is 
equivalent  to  93  per  10,000  ;  whereas,  in  the  general  population,  only 
21  per  10,000  live  to  this  age. 

At  first  sight  this  result  appears  to  be  in  contradiction  with  the  con- 
clusion previously  arrived  at,  that  the  relatives  of  cancer  patients  are 
specially  liable  to  pulmonary  tubercle  ;  but,  it  must  be  borne  in  mind, 
that  these  cancer  families  are  generally  exceedingly  numerous.  Striking 
confirmatory  evidence  is  furnished,  by  inquiring  into  the  family  history 
of  centenarians  and  aged  persons  ;  whence  it  appears,  that  a  large  pro- 
portion of  these — 20  per  cent,  in  the  case  of  females — are  the  surviving 
members  of  phthisical  families.  It  is  evident,  therefore,  that  the  con- 
stitutional peculiarity  which  is  associated  with  tubercle,  is  by  no  means 
incompatible  with  longevity. 

6.  Equally  conclusive  is  the  evidence  as  to  the  great  fecundity  of  cancer  • 
families. 

Thus,  110  of  these  mammary-cancer  families,  averaged  8-8  members  f 
in  each  family,  or  968  members  in  all ;  whereas,  according  to  Farr,  in 
the  general  community  the  average  number  to  a  family  at  about  this 
period  was  4-6,  so  that  an  equal  number  of  families  would  include  only 
506  members. 

Inasmuch  as  a  tendency  of  twinning  usually  goes  with  excessive  <> 
fertility,  it  is  probable  that  an  undue  proportion  of  twins  occurs  in 
these  cancer  families,  as  Critzmann  has  indicated ;  and  this  is  quite  in 
accord  with  other  facts  ascertained  by  me,  as  to  the  sexual  life  of  female 
cancer  patients,  to  which  I  have  previously  referred,  viz.,  early  puberty 
early  marriage,  great  fertility,  late  climacteric  etc. 


374  THE  NATURAL  HISTORY  OF  CANCER 

In  support  of  his  thesis,  Critzmann l  has  related  the  following  remark- 
able history,  in  which  those  of  the  family  who  were  not  twins,  died  of 

The  mother  died  of  cancer  of  the  breast,  after  having  given  birth  to 
twins  (A)  ;  and  one  daughter  (B),  who  died  of  phthisis. 

Both  of  the  twins  died  of  non-cancerous  disease. 

One  of  these  twins  had  a  daughter  (A'),  who  died  of  cancer  of  the 
breast ;  and  her  child  (A"),  died  of  cancer  of  the  stomach. 

This  last  child  (A*)  gave  birth  to  a  daughter  (E),  who  died  of  cancer 
of  the  stomach  ;  and  to  two  twins  (C)  and  (D),  both  of  whom  were  free 
from  cancer,  and  lived  to  a  considerable  age. 

The  twin  (C)  had  three  children,  of  whom  one  daughter  died  of  cancer 
of  the  stomach  and  ovary,  and  another  daughter  of  cancer  of  the 
stomach.  The  latter  gave  birth  to  a  son,  who  died  of  cancer  of  the 
testis ;  and  to  a  daughter,  who  was  alive  and  well,  when  seen  by  the 
author,  being  the  mother  of  two  pairs  of  twins,  all  of  whom  were  alive 
and  well. 

The  twin  (D)  died  childless. 

I  have  often  had  occasion  in  the  course  of  this  work,  to  refer  inci- 
dentally to  the  analogies  between  local  anomalies  per  excessum,  and 
tumours — malignant  and  non-malignant — pointing  out  that  no  sharp 
line  of  distinction  can  be  drawn  between  them,  without  arbitrarily 
severing  the  chain.  In  this  connexion,  it  is  interesting  to  find  that  a 
similar  kind  of  alternation  of  twins  with  local  anomaly  per  excessum,  has 
been  noted  by  F.  Galton ;  2  thus,  referring  to  a  family  remarkable  for  its 
twins,  he  says  :  "  Whenever  single  children  were  born,  they  always  had 
six  fingers  and  six  toes  ;  but,  the  sets  of  twins,  never  had."  In  both 
these  families  we  evidently  have  to  do  with  constitutional  tendency  to 
over-development,  manifesting  itself  in  various  forms,  e.g.,  in  twins,  in 
anomaly  per  excessum,  and  in  cancer. 

The  foregoing  conclusions  as  to  the  influence  of  heredity  in  cancer, 
although  based  mainly  upon  facts  derived  from  the  study  of  the  family 
history  of  women  with  cancer  of  the  breast  and  uterus,  are,  never- 
theless, as  I  have  specially  ascertained,  equally  valid  for  cancer  of  all 
parts  of  the  body. 

In  the  present  transitional  state  of  fundamental  conceptions  relating 
to  physiological  heredity,  it  seems  best  to  abstain  from  interpreting  the 
facts  adduced  in  this  chapter  in  terms  of  the  Mendelian  theory  ;  although 
I  believe  the  time  will  soon  come,  when  it  will  be  advantageous  to  review 
the  subject  from  this  standpoint.  Even  now  it  seems  clear  that  the  great 
prophylactic  question  is :  How,  in  breeding,  to  render  a  dominant 
tendency  to  cancer,  recessive  ? 

At  any  rate,  it  is  perfectly  evident  from  what  has  been  stated  in  the 
course  of  this  chapter,  that  those  pathologists  whose  horizon  does  not 
extend  beyond  cells  and  microbes,  have  overlooked  the  chief  factor  in 
the  cancer  problem— that  is  to  say,  predisposition. 

1  Butt.  Mid.,  November  7,  1894. 

2  Journal  of  the  Anthropological  Institute,  1876,  vol.  v.,  p.  327. 


CHAPTER  XVIII 

THE  INITIAL  SEATS  OF  TUMOURS,  AND  THEIR  RELATIVE 
FREQUENCY 

JUST  as,  under  physiological  conditions,  every  organ  and  part  of  the 
body  has  its  proper  life  or  autonomy  ;  so,  under  pathological  conditions, 
each  organ  and  part  likewise  manifests  an  individuality  of  its  own,  the 
effect  of  which  is  very  noticeable  in  the  structure  and  qualities  of  every 
kind  of  tumour  arising  from  it. 

The  much  greater  frequency  with  which  tumours  arise  in  some  organs 
and  parts  of  the  body  than  in  others,  is  an  illustration  of  this  ;  and,  even 
within  the  limits  of  particular  localities,  areas  unduly  prone  to  tumour 
formation  can  always  be  discriminated. 

Hence,  no  study  of  the  life-history  of  tumour  processes  can  be  com- 
plete, which  ignores  pre-existing  structural  peculiarities. 

Perhaps  the  most  generalized  statement  that  can  be  made  about  these 
tumour  areas  is  :  that  they  are  parts  of  the  body  unusually  rich  in 
cellular  elements,  still  capable  of  growth  and  development. 

In  a  previous  chapter,1 1  have  pointed  out  that  the  localities  specially 
prone  to  originate  malignant  tumours  in  infancy  and  early  life,  are  very 
different  from  those  whence  such  tumours  are  apt  to  arise  at  later  periods ; 
and,  for  further  particulars  relating  to  these,  reference  may  be  made  to 
that  writing. 

The  following  investigation  as  to  the  initial  seats  of  tumours  and  their 
relative  frequency,  in  adult  life,  is  based  upon  data  derived  from  the 
annual  reports  of  the  registrars  of  four  large  London  hospitals  (Middlesex, 
University  College,  St.  Bartholomew's  and  St.  Thomas'),  during  a 
period  of  from  sixteen  to  twenty-one  years. 

The  analysis  comprises  15,481  consecutive  examples  of  primary 
tumours  of  all  parts  of  the  body,  in  persons  of  both  sexes ;  and  it  shows 
that  their  site  incidence  and  distribution  were  as  follows  : — 

1  Chapter  ^XV. 
375 


376 


THE  NATURAL  HISTORY  OF  CANCER 


TABLE  I. 

SHOWING  THE  RELATIVE  FREQUENCY  OF  THE  DIFFERENT  VARIETIES 
OF  TUMOURS. 


Kind  of  Tumour. 

Total 
Number  of 

Males. 

Females. 

Males. 
Per  Cent. 

Females. 
Per  Cent. 

Cases. 

Epithelioma     (vel    Carci- 
noma) 

7878 

2861 

5017 

36 

64 

Sarcoma  l  . 

1350 

702 

648 

52 

48 

Fibroma     . 

1661 

176 

1485 

10 

90 

Liporna 
Adenoma   . 

561 
505 

173 

58 

388 
447 

31 
11 

69 

89 

Papilloma  . 

386 

137 

249 

35 

65 

Osteoma    . 

261 

117 

144 

45 

55 

Chondroma 

81 

41 

40 

51 

49 

Angioma    .  .          .  . 
Cystoma2  .. 

157 

1640 

65 
449 

92 
1191 

41 
27 

59 
73 

Unclassified  3 

1001 

412 

589 

41 

59 

Total 

15,481 

5191 

10,290 

33 

67 

From  this  table  I  have  deduced  the  following  percentages,  showing 
the  proneness  of  the  different  tissue  systems  to  originate  tumours. 


TABLE  II. 

SHOWING  THE  RELATIVE  PROCLIVITY  OF  THE  TISSUE  SYSTEMS  TO 

TUMOUR  FORMATION. 

Per  Cent. 

{Epithelioma  (vel  carcinoma)     . .          . .  54'5 

Adenoma              . .          . .          . .          . .  3'5 

Papilloma              2'6 

Cystoma                11'4 

(Sarcoma  (including  myxoma)  . .          . .  9'4 

Fibroma  (including  myofibroma)          . .  11 '5 

Lipoma 3'8 

|  Osteoma               .,          1'8 

I  Chondroma           . .          . .          . .          . .  0"5 

\.  Angioma    . .          . .          . .          . .          . .  I'O 


Epithelial  tumours  (72  per  cent.) 


Connective-tissue  tumours  (28  per 
cent.) 


A  notable  fact  brought  out  by  this  analysis  is,  that  of  the  two  great 
tissue  systems,  the  epithelial  originates  tumours  much  more  frequently 
than  the  connective — the  proportion  being  72  per  cent,  of  the  former  to 
28  per  cent,  of  the  latter. 

A  further  examination  of  the  figures  shows  that  this  great  preponder- 

1  Including  50  cases  of  myxoma  (males  25,  females  25) ;  and  24  of  keloid  (males  11, 
females  13). 

2  Non-congenital  cysts,   1,505  (male  392,  females  1,113— ovarian  635)  ;    congenital 
cysts,  135  (males  57,  females  78). 

3  Cerebral,  248   (males  135,  females  113) ;   cerebellar  39    (males  22,  females    17) ; 
spinal  cord,  6  (males  3,  females  3) ;  mediastinal.  107  (males  73,  females  34)  ;  cutaneous 
moles,  36  (males  12,  females  24). 


THE  INITIAL  SEATS  OF  TUMOURS 


377 


ance  of  epithelial  tumours,  is  entirely  due  to  the  large  excess  of  malignant 
forms  (epithelioma) — the  ratio  being  54-5  per  cent,  of  the  latter,  to 
9-4  per  cent,  of  malignant  connective-tissue  tumours  (sarcoma). 

On  the  other  hand,  of  non-malignant  tumours  only  17-5  per  cent,  are 
derived  from  the  epithelial,  as  compared  with  18-5  per  cent,  from  the 
connective  tissue. 

Or,  it  may  be  stated  in  this  way  :  54-5  per  cent,  of  all  tumours  are 
epitheliomas  (vel  carcinomas)  ;  9-4  per  cent,  sarcomas  ;  24-7  per  cent. 
non-malignant  tumours  ;  and  11-4  per  cent,  cysts. 

Now,  of  all  the  tissues  of  the  body,  the  epithelial  ones  have  on  the 
whole  departed  less  from  the  primordial  type  than  any  others,  hence 
their  cells  still  retain  their  primitive  powers  of  growth  and  multiplica- 
tion in  a  higher  degree  than  others  (dementi  labili)  :  it  is  to  this  that  I 
attribute  their  great  proneness  to  originate  tumours  under  pathological 
conditions. 

In  this  connexion,  some  observations  of  Ribbert's  are  of  import- 
ance. He  has  shown  that  cancer  is  most  prone  to  arise  from  epithelia, 
in  which  active  mitotic  changes  are  normally  always  present,  or  in 
which  such  changes  manifest  themselves  under  certain  physiological 
conditions  (as  in  the  mammae  and  uterus)  ;  whereas,  in  organs  whose 
epithelia  seldom  exhibit  mitoses,  such  as  the  salivary  glands,  lachrymal 
glands,  thyroid,  thymus,  male  mammae  etc.,  cancers  seldom  arise.  These 
observations  give  direct  anatomical  support  to  the  doctrine  I  have  long 
advocated  on  other  grounds — viz.,  that  cancers  and  other  tumours  are 
most  prone  to  arise  in  localities  where  cells  still  capable  of  growth  and 
development  most  abound. 

With  regard  to  the  localities  most  prone  to  tumour  formation,  my 
analysis  of  hospital  cases  yields  the  following  results  : — 


TABLE  III. 

.4.— SHOWING  THE  RELATIVE  FREQUENCY  OF  TUMOURS  AND  THEIR] 
CHIEF  SEATS  IN  PERSONS  OF  BOTH  SEXES. 


Per  Cent. 
Uterus      19'2 
Mamma    17'5 

Skin                                                                               9-4. 

Connective  tissue  (genera 
Tongue  and  mouth 
Ovary       
External  genitalia 
Bones  (ex  maxilla) 

1)       - 

.       7-7 
6'3 
6'8 
o'l 
4-0 
3'3 

Maxilla     
Stomach 
Lower  lip 
All  other  localities 

2'9 
2'6 
2'6 
13'6 

lOO'O 


Of  these  tumours,  19-6  per  cent,  arose  from  some  part  of  the  alimentary 
tract — the  greatest  number  from  the  tongue  and  mouth. 


378 


THE  NATURAL  HISTORY  OF  CANCER 


TABLE  III.  (continued). 

£ -SHOWING  THE  RELATIVE  FREQUENCY  OF  TUMOURS  AND  THEIR 
CHIEF  SEATS  IN  MALES. 

Per  Cent. 


15-9 
9'4 
7'3 
6'1 
6-1 
5-0 
4'8 
3'9 
3'4 
3-1 
2*0 
0'5 
0'2 
15'9 

Connective  tissue  (general) 

Maxilla     

Testis 

Mamma 
Prostate    

All  other  localities 

lOO'O 

41-7  per  cent,  of  these  tumours  originated  in  the  alimentary  tract — 
the  greatest  number  from  the  tongue  and  mouth. 

C.— SHOWING  THE  RELATIVE  FREQUENCY  OF  TUMOURS  AND  THEIR 
CHIEF  SEATS  IN  FEMALES. 

Per  Cent 


Mamma 
Ovary       

Connective  tissue  (general) 
Skin          
External  genitalia 
Bones  (ex  maxilla) 

• 

26'0 
8'7 
6'9 
5'9 
4'6 
2-9 
2'5 

Maxilla     
Tongue  and  mouth 
Brain 

2'4 

1'6 

1*4 

Stomach 
Liver 
All  other  localities 

1'4 
T2 

5-8 

lOO'O 

Of  these  tumours,  8-7  per  cent,  originated  from  the  alimentary  tract — 
the  greatest  number  from  the  rectum. 

These  figures  show  the  great  frequency  with  which,  in  females,  the 
reproductive  organs — uterus,  mamma,  ovary  etc. — are  attacked ;  in 
fact,  nearly  70  per  cent,  of  all  tumours  in  women  arise  from  these  organs. 
The  very  great  frequency  with  which  the  uterus  and  mamma  are  affected, 
is  particularly  striking.  From  the  fact  that  both  of  these  parts  are 
subject  to  remarkable  post-natal  developmental  changes,  it  may  be 
inferred  that  they  are  unusually  rich  in  cells  still  capable  of  growth  and 
multiplication  ;  and  it  is  to  this  that  I  ascribe  their  greater  proclivity  to 
tumour  formation. 

It  accords  with  this,  that  tumours  rarely  originate  from  obsolete  or 
obsolescent  structures  ;  e.g.,  male  breast,  gall-bladder,  clitoris,  hymen, 
thymus,  adrenals,  intervertebral  disks,  membrana  nictitans,  uterus 
masculinus,  Meckel's  diverticulum,  vermiform  appendix,  tendons,  liga- 


THE  INITIAL  SEATS  OF  TUMOURS 


379 


ments,  central  canal  of  nervous  system,  chorda  dorsalis,  urachus, 
coccyx,  os  centrale,  sesamoid  bones,  cartilage  etc. 

It  is  equally  exceptional  for  tumours  to  arise  from  highly  specialized 
structures  such  as  the  heart,  large  bloodvessels,  voluntary  muscles, 
nerves  etc. 

In  all  such  instances  as  the  foregoing,  proliferous  cells  are  scanty  or 
absent ;  and  it  is  to  this  peculiarity  that  their  comparative  immunity  from 
tumour  growth  may  be  ascribed. 


Epithelioma  (vel  Carcinoma). 

Throughout  the  body  malignant  tumours  occur  with  greater  relative   v 
frequency  than  non-malignant  ones  ;  I  have  found  the  ratio  to  be  64  per 
cent,  of  the  former,  to  36  per  cent,  of  the  latter. 

Of  26,722  fatal  malignant  tumours  (males  10,476,  females  16,246) 
tabulated  in  the  national  mortality  statistics  for  1900,  only  1,611  (males 
790,  females  821)  are  discriminated  as  sarcoma,  or  6  per  cent. ;  whereas, 
of  my  9,228  hospital  malignant  tumours,  1,350  were  sarcomatous,  or 
14-6  per  cent.,  and  7,878  epitheliomatous,  or  85-4  per  cent. 

Of  the  13,824  tumours  of  all  kinds — the  localizations  of  which  are 
defined  in  my  table — 7,297  were  of  the  malignant  epithelial  type  (males 
2,669,  females  4,628). 

These  were  distributed  as  follows  : — 

TABLE  IV. 

SHOWING  THE  LOCALIZATION  OF  MALIGNANT  EPITHELIAL  TUMOURS 
IN  MALES  AND  FEMALES,  AS  INDICATED  BY  HOSPITAL  STATISTICS. 

MALES  (2,669  CASES). 


Tongue  and  mouth 
Skin          
Lip            
Stomach 
Rectum 
External  genitalia 
(Esophagus 
Liver 

26'3 
14-3 
12'2 
8'3 
7'5 
6-8 
5'3 
4'4 
1'9 
0'6 
0'3 
121 

lOO'O 
*n-3 

Intestines 
Breast       
Prostate    
All  other  localities 

FEMALES 
Breast 

(4,628 

CASES). 

Uterus       ..          ..                      34'0 
Rectum    ....                        .            .                   4'3 
Skin          ....                        .            .            .4-1 
External  genitalia                        .            .            .       3'4 
Stomach                                                                        2'8 

Liver         ....                        .            .            .       2'5 
Tongue  and  mouth                        .            .                   2'  18 
Intestines             ..                        .            .                   TOG 
(Esophagus          .  .                        ...       0'70 
Lip                                                                                0'06 

All  other  localities          4'60 

100-00 


THE  NATURAL  HISTORY  OF  CANCER 


This  analysis  shows  that  a  large  proportion  of  all  malignant  epithelial 
tumours  (epitheliomas),  originate  from  some  part  of  the  alimentary 
tract— the  percentage  being  41-9,  some  of  which  are  not  specially  dis- 
criminated in  the  table. 

The  liability  of  males  to  epithelioma  of  this  system  is  particularly 
great,  no  less  than  68-6  per  cent,  of  all  their  malignant  epithelial  tumours 
being  thus  located  ;  whereas,  15-2  per  cent,  is  the  proportion  for  females. 

In  women,  mammary  (40-3  per  cent.)  and  uterine  (34  per  cent.)  forms 
of  the  disease  are  predominant ;  but,  in  men,  the  corresponding  localities 
are  seldom  affected — mamma,  0-6  per  cent.  ;  prostate,  0-3  per  cent. 

On  the  other  hand,  in  the  tongue  and  mouth,  skin,  and  lower  lip, 
the  proclivity  of  men  is  much  greater  than  that  of  women. 

The  same  subject  from  another  standpoint,  is  further  iUustrated  by 
the  following  data  : — 

TABLE  V. 

SHOWING  THE  LOCALIZATION  OF  MALIGNANT  EPITHEUAL 
TUMOURS  IN  BOTH  SEXES. 


Males. 

Females. 

Total. 

Breast             

16 

1863 

1879 

Uterus  and  prostate  .  . 

7 

1571 

1578 

Tongue  and  mouth    .  . 

703 

101 

804 

Skin     .. 

381 

190 

571 

Rectum 

199 

202 

401 

Stomach 

222 

130 

352 

External  genitalia 
Lip  (lower) 

182 
326 

158 
3 

340 
329 

Liver   .  .           .           . 

115 

113 

228 

(Esophagus 

144 

35 

179 

Intestines 

49 

49 

98 

Superior  maxilla 

42 

28 

70 

Bladder 

43 

16 

59 

Testis  and  ovary 

27 

27 

54 

Larynx 

34 

4 

38 

Anus 

17 

10 

27 

All  other  localities     .  . 

162 

128 

290 

Total   .. 

2669 

4628 

7297 

This  shows  that  of  1,879  consecutive  cases  of  mammary  cancer  in 
both  sexes,  only  16  were  of  the  male  breast,  or  1  in  117  ;  similarly  only 
7  prostatic  cancers  were  met  with  to  1,571  uterine  cancers,  or  1  in  224. 

On  the  other  hand,  of  329  consecutive  lower-lip  cancers  only  3  were 
in  females,  or  1  in  108  ;  similarly  with  regard  to  the  tongue  and  mouth, 
of  804  consecutive  cancers  only  101  were  in  females,  or  1  in  7. 

The  foregoing  data  may  be  relied  upon  as  representing  the  localiza- 
tion of  the  disease  in  hospital  patients,  but  this  of  course  implies  a  certain 
selection.  Owing  to  this  cause,  the  relative  frequency  of  the  disease 
in  such  localities  as  the  breast,  tongue,  mouth,  skin  and  lip,  is  probably 
exaggerated;  while  the  liability  of  the  stomach,  liver  and  intestines 
is  no  doubt  understated. 


THE  INITIAL  SEATS  OF  TUMOURS 


381 


To  correct  these  shortcomings  in  the  clinical  data,  I  append  some  of 
the  chief  results  deducible  from  the  national  mortality  statistics,1  which 
refer  to  malignant  disease  in  general. 

Owing  to  a  certain  laxity  in  death  certification  etc.,  these  estimates 
are  confessedly  not  perfectly  reliable  ;  but,  the  basis  on  which  they  rest 
is  so  broad,  that  —  in  spite  of  this  defect  —  they  furnish  valuable 
indications. 

TABLE  VI. 

SHOWING  THE  LOCALIZATION  OF  MALIGNANT  DISEASE  IN  MALES  AND 
FEMALES,  AS  INDICATED  BY  MORTALITY  RETURNS  (ENGLAND  AND 
WALES). 


MALES  (9,932  CASES). 

Stomach 

Liver  and  gall-bladder  . . 

Rectum 

Tongue  and  mouth 

Intestines  (ex  rectum)   . . 

(Esophagus 

Skin 

Bladder 

Jaws 

Face 

Pharynx 

Larynx  and  trachea 

Lips 

Testis  and  penis 

Prostate 

Breast 

All  other  localities 


FEMALES  (15,264  CASES). 


Per  Cent. 

.     21-4 

Uterus      .  . 

134 

Breast 

9'6               Liver  and  gall-bla 
6'4              Stomach  .  . 

dder  .' 

6-1 

Rectum    .. 

6'0 

Intestines  (ex  rec 

ium)  . 

4-1 

Abdomen 

2-8 

Peritoneum 

2-7 

Ovary 

2-0 

(Esophagus 

2'0 

Skin 

1'8 

Bladder    .. 

T6 

Jaws 

1-6 

Face 

i-o 

Tongue  and  mouth 

0-2 

Lips          

17'3 

All  other  localities 

lOO'O 


PerCent. 

23-5 

15-8 

13-5 

13-2 
5'3 
5-2 
2-0 


1-5 
I'O 
0'9 
0-8 
0-6 
0'6 
0-2 
12-5 

lOO'O 


This  table  makes  it  quite  plain,  that  cancer  is  a  disease  chiefly  pre- 
dominant in  the  alimentary  tract. 

Of  25,196  cancers — in  persons  of  both  sexes — comprised  in  these 
returns,  no  less  than  13,627  were  of  the  alimentary  tract,  or  54  per  cent. 

Among  the  males,  70-6  per  cent,  were  affected  with  alimentary 
cancer  ;  and  among  the  females  43-3  per  cent. 

Uterine  and  mammary  cancer  together,  account  for  39-3  per  cent, 
of  the  female  cancer  mortality. 

It  will  be  noticed  that  malignant  disease  of  the  liver,  occupies  a  very 
exalted  position  in  these — and  in  fact  in  all — mortality  returns. 

There  is  great  diversity  of  opinion  among  pathologists,  as  to  the 
frequency  of  primary  malignant  disease  of  the  liver :  some  think  that 
it  is  common,  and  others  that  it  rarely  occurs.  The  truth  probably  lies 
between  these  extremes.  Secondary  cancer  of  the  liver  is  certainly  of 
vastly  more  frequent  occurrence,  than  the  primary  form  ;  and  it  is  often 
difficult  clinically  to  discriminate  between  the  two.  Owing  to  this 
cause,  the  frequency  of  primary  malignant  disease  of  the  liver  is  no  doubt 
overstated  in  the  national  mortality  statistics  ;  but,  even  when  allowance 
has  been  made  for  errors  of  this  kind,  I  believe  the  mortality  from  this 
cause  is  considerable. 

1  Sixty-first  Annual  Report  of  the  Registrar-General  for  England  and  Wales. 


382  THE  NATURAL  HISTORY  OF  CANCER 

In  further  illustration  of  this  subject,  I  give  below  the  chief  results 
of  an  analysis  of  the  United  States  mortality  returns,  as  detailed  in  the 
Twelfth  United  States  Census  Report  for  the  year  1900. 

TABLE  VII. 

SHOWING  THE   LOCALIZATION  OF  CANCER  IN  MALES  AND  FEMALES,  AS 
INDICATED  BY  THE  MORTALITY  RETURNS  (UNITED  STATES). 


MALES. 

FEMALES. 

Per  Cent. 

Per  Cei 

43-0 
.      14T) 

Uterus      . 
Stomach  . 

.     27-6 
.     24-4 

Head,  face,  and  neck     .  . 

.     10-4 

Breast      . 

.     15-7 

Tongue,  mouth,  and  throat 
Abdomen 
Rectum 

9'5 
9-2 
5'4 

Liver 
Abdomen 
Rectum    . 

.     12T) 

.       7'6 
.       3-5 

Bladder 

2'5 

Head,  face 

and  neck     . 

.       3-1 

Larynx     
Breast 

I'O 
0-7 

Tongue,  mouth,  and  thn 
Ovary 

at 

.        1-6 

.       0'9 

Penis 

0'3 

Bladder    

.       0-6 

Testis 

O'l 

Larynx 

.       O'l 

All  other  localities 

3'4 

All  other  localities 

.       2'4 

liWA 

irwvn 

This  table  shows  even  greater  predominance  of  cancer  of  the 
alimentary  tract,  than  the  English  one — 66-7  per  cent,  of  all  cancers  in 
both  sexes  being  thus  situated. 

Of  the  male  cancer  mortality  81-6  per  cent,  was  of  the  alimentary 
system,  and  of  the  female  cancer  mortality  51-8  per  cent. 

The  Proclivity  of  Certain  Regions  in  Particular  Organs  etc. 

Another  matter  deserving  notice  in  this  connexion,  is  the  great  pro- 
clivity of  certain  regions  of  particular  organs  to  cancer  and  tumour 
formation,  and  the  comparative  immunity  of  other  regions. 

Even  the  different  tissue  constituents  of  the  various  organs,  vary 
greatly  in  this  respect ;  and  that  when  they  are  genetically  akin. 

Thus,  while  countless  thousands  of  cancers  have  sprung  from  the 
uterine  mucosa,  I  know  of  only  a  very  few  instances  in  which  the  disease 
has  originated  from  its  peritoneal  lining. 

Again,  the  mucosa  of  the  lower  segment  of  the  uterus  (cervix  etc.) 
is  very  much  more  apt  to  generate  cancer,  than  that  of  its  upper  segment 
(corpus) — the  percentage  proportion  being  97  per  cent,  in  the  former 
locality,  to  3  per  cent,  in  the  latter. 

Strange  to  relate,  the  proclivity  of  the  uterine  musculature  to  originate 
myoma  in  its  upper  and  lower  segments,  is  just  the  converse  of  that  of 
its  mucosa  to  originate  cancer  ;  for,  while  over  90  per  cent,  of  all  uterine 
myomata  originate  in  the  corpus,  only  about  10  per  cent,  spring  from  the 
cervix. 

Another  illustration  of  the  same  peculiarity  is  seen,  in  the  great  diver- 
sity in  liability  to  cancer  and  other  tumours,  manifested  by  the  various 
organs  evolved  from  the  different  segments  of  the  Miillerian  ducts.  Of 
these  organs,  only  the  uterus  manifests  great  proclivity  to  tumour 
formation — for  the  vagina  and  Fallopian  tubes  are  seldom  affected. 

Thus,  of  9,227  consecutive  tumours  in  women  tabulated  by  me, 


THE  INITIAL  SEATS  OF  TUMOURS  283 

2,648  were  of  uterine  origin  (cancer  1,571,  sarcoma  2,  myoma  1,073, 
and  cystoma  2)  ;  but  only  54  arose  from  the  vagina  (cancer  40,  sarcoma'2, 
myoma  3,  and  cystoma  9)  ;  while,  not  a  single  case,  is  credited  to  the 
Fallopian  tubes  !  1 

From  this  it  may  be  inferred,  that  the  biological  peculiarities  which 
determine  a  given  part  to  tumour  formation,  depend  more  upon  functional 
than  upon  genetic  considerations  ;  the  vagina,  for  instance,  is  physio- 
logically more  akin  to  the  vulva  than  to  the  uterus,  and  the  results  of 
this  similarity  are  apparent  in  its  pathological  neoplastic  variations. 

In  other  parts  of  the  body  similar  conditions  prevail. 

Thus,  in  the  female  breast,  cancerous  tumours  are  much  more  prone 
to  develop  in  some  parts  of  the  organ  than  in  others. 

The  extreme  rarity  of  epithelial  cancer  of  the  nipple  and  areola  is, 
for  instance,  very  remarkable ;  for,  as  we  have  seen,1  less  than  1  per  cent, 
of  all  mammary  cancers  thus  originate.  Cancer  arising  from  any  other 
part  of  the  mammary  integument  is  so  exceedingly  rare,  that  neither 
Velpeau  nor  Billroth,  with  their  large  clinical  experience,  ever  met  with 
a  single  instance  ;  and  the  number  of  such  cases  even  now  on  record  is 
less  than  a  dozen. 

Again,  cancerous  tumours  of  the  mamma  form  much  oftener  in  the 
peripheral,  than  in  the  central  part  of  the  gland.  Of  132  cases  under  my 
observation,  in  90  (68  per  cent.)  the  tumour  was  peripheral ;  and  in 
42  (32  per  cent.)  central.  This  accords  with  what  I  have  previously 
pointed  out,  as  to  the  special  tendency  of  cancers  to  arise  in  the  seats 
of  greatest  post-embryonic  developmental  activity,  where  cells  still 
capable  of  growth  and  development  most  abound  ;  that  is  to  say,  in 
the  immediate  vicinity  of  the  acini  and  smallest  ducts,  which  are  much 
more  numerous  in  the  peripheral  than  in  the  central  part  of  the  gland. 
Here  it  may  be  mentioned,  that  the  great  majority  of  mammary  cancers 
are  acinous  derivatives,  while  only  a  small  minority  spring  from  the 
tubular  structures  of  the  gland,  and  hardly  any  from  the  large  ducts. 

With  regard  to  the  localization  of  the  peripherally  situated  cancers, 
most  of  them  are  met  with  in  the  upper  and  axillary  mammary  seg- 
ments. Thus,  of  90  cases  under  my  observation,  the  disease  was  situated 
in  the  upper  segment  in  46,  in  the  axillary  in  20,  and  in  the  sternal  in  3. 
Gross'  analysis  of  the  localization  of  820  cancerous  tumours  of  the  mamma, 
may  be  diagrammatically  represented  as  follows  : — 

Upper. 

206  90  55 

Axillary.     83  231  32     Sternal. 

32  51  40 

Lower. 

A  considerable  number  of  these  peripheral  cancers,  are  situated  quite 
outside  the  mammary  gland ;  where,  as  I  have  elsewhere  shown,2  they 
originate  from  outlying  sequestrated  mammary  structures,  which  are  of 
common  occurrence  in  this  organ  and  in  its  vicinity. 

I  was  able  to  determine  that  this  was  the  condition  in  13  (9-8  per 

1  Chapter  XI. 

2  "  Diseases  of  the  Breast,"  1894,  chap,  iv.,  p.  73  :  "  Paramammary  Tumours  arising 
from  Supernumerary  Mammary  Structures." 


384  THE  NATURAL  HISTORY  OF  CANCER 

cent.)  out  of  132  consecutive  breast  cancers  under  my  observation. 
Of  29  tumours  that  originated  in  this  way,  15  were  situated  in  the  axilla, 
8  in  the  sternal  region,  and  6  were  found  above  the  breast. 

The  different  segments  and  organs  of  the  digestive  system  manifest 
similar  inequalities,  in  their  proclivity  to  malignant  epithelial  tumours. 
Thus,  as  the  national  mortality  returns  show,  the  localization  per- 
centages of  the  disease  in  this  system— in  males— are  as  follows  :— 
stomach  30-3,  intestines  22-3,  liver  19-1,  tongue  and  mouth  9,  oesophagus  6, 
abdomen  and  peritoneum  3-8,  pharynx  2-9,  lips  2-3,  and  pancreas  1-7. 

If  we  take  these  segments  of  the  alimentary  canal  separately,  each 
will  be  found  to  present,  within  its  own  limits,  similar  diversities  in  pro- 
clivity to  cancer. 

Thus,  in  the  stomach,  the  pylorus  is  attacked  with  much  greater  fre- 
quency than  any  other  part  of  the  organ,  for  Brinton  and  Welch's  analysis 
of  1,524  cases — in  which  the  seat  of  the  disease  was  well  denned — shows 
that  no  less  than  66-3  per  cent,  of  all  gastric  cancers  were  thus  situated. 
Other  parts  of  this  organ  are  affected  in  the  following  percentage  pro- 
portions : — lesser  curvature  12-2,  cardia  9-2,  posterior  surface  5-2,  great 
curvature  2-9,  anterior  wall  2-7,  fundus  1-2,  and  centre  0-3. 

Inequalities  of  this  kind  are  still  more  strikingly  illustrated,  in  the 
incidence  of  intestinal  cancer. 

Here  one  is  at  once  struck  with  the  great  predominance  of  the  disease 
in  the  rectum — 61  per  cent,  of  all  intestinal  cancers  being  thus  located, 
according  to  the  mortality  returns.1  On  the  other  hand,  only  5  per  cent, 
of  all  intestinal  cancers  arise  from  the  great  length  of  the  small  intestine — 
the  duodenum  being  very  rarely  affected. 

Of  the  remaining  34  per  cent.,  one-half  (17  per  cent.)  are  located  in 
the  sigmoid  flexure ;  and  the  other  half  are  nearly  equally  distributed 
between  the  other  segments  of  the  colon — with  decided  predominance 
in  the  descending  colon.  The  caecum  and  ileo-caecal  valve  are  rarely 
affected,  and  the  appendix  hardly  ever — in  fact,  the  percentage  for  all 
these  parts  taken  together,  hardly  amounts  to  0-5. 

In  the  rectum  itself  similar  phenomena  are  met  with  ;  for,  I  have 
found  that  54-5  per  cent,  of  all  cancers  of  this  part,  originate  at  from 
2  to  4  inches  above  the  anus  ;  while  about  5  per  cent,  of  all  intestinal 
cancers  are  anal  in  origin. 

In  the  tongue,  I  find  that  malignant  tumours  almost  invariably  arise 
from  the  epithelial  elements,  and  hardly  ever  from  those  of  the  much  more 
abundant  connective  tissue ;  thus,  of  644  primary  malignant  tumours  of 
the  tongue  in  my  list,  all  but  one  (sarcoma)  were  of  epithelial  origin. 

Moreover,  it  is  noteworthy  that  of  the  epithelial  elements  of  the 
tongue,  it  is  only  the  epidermoidal  that  originate  malignant  tumours  ; 
the  numerous  epithelial  glandular  structures  of  this  organ,  hardly  ever 
being  affected  in  this  way.2 

I  have  found  the  seats  of  the  initial  lesions  of  epithelioma  of  the 
tongue  and  mouth,  in  100  consecutive  cases  in  males,  to  be  as  follows  : — 

1  Hospital  data,  tabulated  by  myself,  show  a  still  higher  proportion — viz.,  of  466 
intestinal  cancers,  86  per  cent,  -were  of  the  rectum. 

3  For  reference  to  a  case  of  primary  cancer  of  the  tongue,  which  arose  from  the  mucous 
glands  of  its  surface,  vide,  Miles,  "  Encyclopaedia  Medica,"  p.  290. 


THE  INITIAL  SEATS  OF  TUMOURS 


385 


Edge  of  tongue1  (middle,  21  ;  base,  14  ;  tip,  5  ;  front,  4)    . 

Floor  of  mouth  (near  frsenum) 

Buccal  surface  of  cheek 

Gum 

Dorsum  of  tongue 

Empty  socket  of  molar  teeth 

Soft  palate          

Hard  palate 

Floor  of  mouth  (other  than  near  fraenum) 

Substance  of  tongue 

Between  gum  and  cheek 

Between  gum  and  lower  lip     . . 


Total 


in  48 
21 
10 
5 
4 
2 
2 
2 
2 
2 
1 
1 


100  cases. 


In  the  skin  similar  peculiarities  are  noticeable  ;  but,  in  a  larger  pro- 
portion of  cases,  the  disease  seems  to  start  from  the  glandular  structures. 
Of  49  consecutive  cases  of  cutaneous  cancer  of  which  I  have  preserved 
the  records,  37  originated  from  the  head,  1  from  the  neck,  2  from  the 
trunk,  7  from  a  lower  limb,  and  2  from  an  upper  limb. 

Of  the  37  head  cases,  mostly  rodent  ulcer,  23  originated  from  the 
nose  (near  the  inner  canthus,  10  ;  the  ala,  3  ;  between  the  two  foregoing,  5  ; 
tip  of  nose,  3  ;  root,  1  ;  middle  of  bridge,  1),  6  from  the  cheek,  3  from  the 
lower  eyelid,  2  from  the  forehead,  2  from  the  skin  of  the  upper  lip,  and 

1  from  the  external  ear. 

The  great  predisposition  of  the  skin  of  the  face,  especially  that  of 
the  nose  and  its  vicinity,  to  develop  cancer  is  very  remarkable. 

Of  the  7  cases  of  cancer  of  the  lower  limb,  4  sprang  from  the  thigh, 

2  from  the  foot,  and  1  from  the  knee. 

Of  the  2  upper-limb  cancers,  1  was  of  the  axilla  and  the  other  of  the 
hand. 

Of  the  2  trunk  cancers,  1  sprang  from  the  skin  of  the  back,  and  the 
other  from  that  of  the  front  of  the  abdomen. 

It  has  been  suggested  by  Cheatle,2  that  this  special  proclivity  of 
certain  tissues  and  localities  to  cancer  is,  directly  or  indirectly,  connected 
with  certain  nerve  influences — trophic — which  are  supposed  to  preside 
over  the  affected  areas.  This  suggestion  appears  to  me  to  be  nothing  but 
a  hypothesis  of  a  hypothesis,  for  trophic  nerves  and  trophic  areas  have 
never  been  proved  to  exist ;  and  most  physiologists,  who  have  especially 
studied  the  subject,  reject  this  theory  of  growth.  The  clinical  evi- 
dence is  equally  unconvincing ;  thus,  Gowers  remarks 3 :  "It  was  once 
thought  that  there  are  special  trophic  fibres,  some  think  so  still,  but  evi- 
dence of  their  existence  is  difficult  to  discern."  In  the  early  stages  of  the 
development  ab  ovo,  growth  and  differentiation  go  on  in  a  regular  and 
orderly  manner,  in  the  absence  of  nerves  and  bloodvessels ;  and  there  is 
no  valid  reason  for  supposing  that,  at  subsequent  periods,  growth  is 
differently  regulated.  I  am  certainly  unacquainted  with  any  facts  con- 
nected with  the  localization  of  cancer,  that  really  support  Cheatle's  view  ; 
and,  those  adduced  by  its  author,  seem  to  me  to  be  altogether  inconclusive. 

Such  facts  as  to  the  initial  seats  of  the  disease,  as  I  have  set  forth  in 
this  chapter,  cannot  be  thus  explained  ;  and,  in  the  case  of  secondary 
cancers,  we  can  certainly  eliminate  any  such  hypothetical  influence. 

1  Right  side,  25  ;  left  side,  18. 

2  Transactions  of  the  Pathological  Society,  London,  1903. 

3  Lancet,  1905,  vol.  ii.,  p.  1594.  25 


386  THE  NATURAL  HISTORY  OP  CANCER 

As  I  have  already  intimated,  and  as  I  shall  subsequently  have  occa- 
sion to  show,  these  inequalities  in  morbid  proclivity  have  notliing  what- 
ever to  do  with  nervous  or  vascular  influences  ;  but  they  are  rather  the 
outcome  of  biological  peculiarities  inherent  in  the  cellular  elements  of 
the  affected  parts,  which  ultimately  resolve  themselves  into  functional 
modifications. 

Sarcoma. 

Passing  now  to  the  sarcomas  of  adult  life,  I  find  that  most  of  them 
arise  from  the  bones,  connective  tissue,  and  from  certain  organs. 

My  analysis  of  1,350  primary  sarcomas  in  adults,  shows  that  of  the 
bones,  those  most  prone  to  be  affected  are  the  superior  and  inferior 
maxilla,  the  femur,  humerus,  tibia,  innominate,  scapula,  and  skull  bones. 

Next  to  the  bones,  in  order  of  proclivity,  come  the  female  breast, 
genital  glands,  eye,  parotid  and  skin. 

Sarcomas  of  the  soft  parts  of  the  face,  neck,  thigh,  leg,  orbit  etc.,  are 
also  of  frequent  occurrence. 

The  numbers  for  each  locality,  are  shown  in  the  following  tables  : — 

TABLE  VIII. 

SHOWING  THE  PRIMARY  SEATS  OF  SARCOMA  IN  ADULTS. 

GENERAL  STATEMENT. 


Locality. 

Total. 

Males.               Females. 

Bones 
Connective  tissue 
Other  parts 
Unclassified    .. 

385 
340 
341 
284 

217                    168 
186                   154 
141                   200 
158                   126 

Totals 

1350 

702                   648 

BONES  AFFECTED. 


Locality. 

Total. 

Males. 

Temales. 

Superior  Maxilla 
Inferior  Maxilla 

102 

48 

53 
31 

49 
17 

Femur 

61 

34 

27 

Humerus 

[ 

22 

13 

9 

Tibia 

19 

13 

6 

Innominate 

19 

12 

7 

Skull 

19 

12 

7 

Scapula 

12 

7 

5 

Fibula 

11 

6 

5 

Foot 

6 

5 

1 

Ribs 

6 

5 

1 

Sacrum 

4 

3 

1 

Ulna 

3 

2 

1 

Radius 

3 

3 

Clavicle 

2 

1 

1 

Hand 

2 

2 

Coccyx 

2 

2 

Sternum 

I 

1 

Unclassified 

43 

20 

23 

Totals        

385 

217 

168 

THE  INITIAL  SEATS  OF  TUMOURS 


387 


TABLE  VIII.   (continued). 
CONNECTIVE  TISSUE. 


Locality. 

Total. 

Males. 

Females. 

Face 

20 

12 

8 

Neck 

20 

12 

8 

Thigh 

18 

7 

11 

Leg  .  . 

13 

6 

7 

Orbit 

12 

8 

4 

Mediastinum  .  . 

11 

7 

4 

Peritoneum     .  . 

11 

8 

3 

Multiple 

10 

5 

5 

Nose 

10 

10 

— 

Groin 

8 

7 

1 

Retro-peritoneal 

8 

3 

5 

Arm 

7 

5 

2 

Shoulder 

7 

5 

2 

Scalp 

6 

4 

2 

Abdominal  wall 

6 

3 

3 

Forearm 

5 

2 

3 

Hand 

4 

4 



Popliteal  space 
Upper  lip 

4 
4 

2 
2 

2 

2 

Pelvis 

3 



3 

Peri-renal 

2 

1 

1 

Muscle 

2 

2 

— 

Eyelid 

2 

— 

2 

Foot 

1 



Infra-clavicular 

1 

Scapular 

1 

— 

Back 



1 

Axilla 



1 

Gluteal 

1 

— 

Ischio-rectal   .  . 



1 

Unclassified    .. 

140 

68 

72 

Totals        

340 

186 

154 

Gurlt's  analysis  of  741  sarcomata  gives  analogous  results  :  194  cases 
arose  from  the  maxillae  (superior  96,  inferior  83),  150  from  the  female 
breast,  45  from  the  testis,  33  from  the  parotid,  30  from  the  face,  30  from 
the  thigh,  30  from  the  leg,  26  from  the  neck  and  submaxillary  region, 
20  from  the  inguinal  region,  18  from  the  orbit,  18  from  the  arm,  18  from 
the  foot,  15  from  the  nares,  13  from  the  eye,  7  from  the  ovary  etc. 

Of  162  sarcomata  of  the  long  bones  by  Gross  and  36  by  myself,  the 
initial  seats  of  the  disease  were,  the  femur  in  84,  tibia  in  53,  humerus 
in  29,  fibula  in  13,  ulna  in  7,  radius  in  8,  and  radius  and  ulna  in  1  case. 

Of  128  malignant  melanotic  tumours  of  the  skin  tabulated  by  Dieterich, 
48  arose  from  the  extremities,  41  from  the  trunk,  28  from  the  head,  and 
11  from  the  neck.  Of  Gurlt's  18  melanomata,  5  originated  from  the 
face,  3  from  the  leg,  and  1  each  from  the  parotid  region,  eye,  rectum, 
liver,  ovary,  breast,  abdominal  wall,  hand,  thigh  ;  and  1  was  of  multiple 
origin. 

Of  175  primary  sarcomata  of  the  gastro-intestinal  tract  tabulated  by 
Corner  and  Fairbank,1  the  site  incidence  was  as  follows  : — (Esophagus  14, 

1  Transactions  of  the  Pathological  Society,  London,  1905,  vol.  Ivi.,  p.  25. 

25—2 


THE  NATURAL  HISTORY  OF  CANCER 


TABLE  VIII.    (continued). 
OTHER  PARTS. 


Locality. 

Total. 

Males. 

Females. 

Breast 
Genital  glands 
Eye 
Parotid 

95 
64 
40 
32 

3 

40 
20 
15 

92 
24 
20 
17 

Skin 

17 

7 

10 

Palate 

12 

4 

8 

Lymph-glands 
Kidney 

12 

8 

10 
3 

2 
5 

Rectum 

7 

5 

2 

Bladder 

6 

5 

1 

Tonsil 

5 

5 

— 

Submaxillary  gland 

4 

4 

— 

Lung 
Prostate 

3 
2 

3 
2 

z 

Larynx 

2 

2 

— 

Pharynx 

2 

— 

2 

Vagina 
Uterus 

2 

2 

— 

2 
2 

External  ear  .  . 

1 

— 

Optic  nerve    .  . 
Vulva 

— 

1 

1 

Colon 

1 

— 

Thyroid 

— 

1 

Mouth 

1 

— 

Supra-renal 

1 

— 

Spinal  meninges 

— 

1 

Tongue 

1 

— 

Brain 

1 

_ 

Unclassified    .  . 

16 

7 

9 

Totals        

341 

141 

200 

stomach  58,  small  intestine  65,  ileo-caecal  region  20,  large  intestine  11, 
and  rectum  7. 

Of  the  gastric  sarcomata,  64  per  cent,  originated  from  some  part  of 
the  organ  other  than  the  pylorus,  which  gave  origin  only  to  36  per 
cent. 

In  the  small  intestine,  the  original  seats  of  the  disease  were — ileum  in 
28  cases,  jejunum  in  19,  and  duodenum  in  8. 

This  collection  of  cases  comprises  3  examples  of  primary  intestinal 
melanotic  sarcoma — 2  of  the  rectum,  and  1  of  the  ileum. 

Pure  myxomata — that  is  to  say,  tumours  consisting  of  clear,  glassy, 
translucent  substance,  like  that  of  the  jelly-fish — are  certainly  very 
rare.  I  have  met  with  only  two  or  three  cases  of  this  kind.  Myxomata 
usually  comprise,  besides  their  special  structure,  sarcomatous,  fibrillar, 
chondromatous  or  fatty  elements,  which  tend  to  obscure  their  glassy 
properties.  The  localities  affected  in  my  50  cases,  were  as  follows  :— 
thigh  8  (males  6,  females  2)  ;  parotid  4  (males  3,  female  1) ;  breast  4 
(males  2,  females  2)  ;  peri-renal  2  (male  1,  female  1)  ;  and  1  each  as 
follows :— popliteal  (male),  pectoral  (female),  naso-pharyngeal  (male), 
pelvis  (female),  arm  (female),  neck  (male),  finger  (male),  loin  (male), 


THE  INITIAL  SEATS  OF  TUMOURS  389 

nose  (female),  testis,  soft  palate  (female),  and  unclassified  21  (males  7, 
females  14). 

It  is  interesting  to  note,  as  in  the  case  of  epithelioma,  the  extreme 
rarity  of  sarcoma  in  some  situations,  e.g.,  the  muscles,  tendons,  spleen, 
heart,  great  bloodvessels,  digestive  system,  stomach,  tongue,  uterus  etc. 


Non-malignant  Tumours. 

In  the  case  of  non-malignant  tumours,  similar  diversities  in  morbid 
proclivity  are  noticeable,  as  may  be  gathered  from  the  following 
items  : — 

Leio-myomata  occur  with  extraordinary  frequency  in  the  uterus,  and 
in  the  prostate  ;  but,  in  other  parts  of  the  body,  they  are  of  the  greatest 
rarity,  although  leio-myomatous  tissue  is  widely  diffused. 

Some  pathologists  deny  the  right  of  the  prostatic  tumours  to  be 
classed  as  myomata,  because  of  the  glandular  structures  they  contain  ; 
but,  in  all  parts  of  the  body  where  these  tumours  occur,  it  is  not  uncommon 
to  find  included  glandular  structures. 

Fibromata  usually  present  as  polypoid  outgrowths,  their  commonest 
seats  being  the  uterus  (myo-fibromatous),  maxillse  (epulis),  nasal  fossse, 
lower  limb,  external  genitals,  external  auditory  meatus,  subcutaneous 
(painful  tubercle),  basis  cranii  (naso-pharyngeal),  skin  etc. 

Lipomata  may  be  either  acquired,  or  they  may  already  exist  at  birth. 
The  latter  variety  is  comparatively  rare.  Of  200  consecutive  acquired 
lipomata,  all  but  5  were  situated  in  the  subcutaneous  panniculus 


The  other  five  were  more  deeply  seated,  either  under  or  between  the 
adjacent  muscles.  In  5  out  of  190  cases,  more  than  a  single  tumour  was 
present. 

The  situations  occupied  by  these  tumours  were  as  follows  : — trunk 
47-8  per  cent. — rather  more  than  half  being  situated  posteriorly,  chiefly 
in  the  lumbar  and  scapular  regions  :  upper  limb  27-8  per  cent. — most  of 
them  being  in  the  deltoid,  acromial  and  axillary  regions  :  lower  limb 
12-2  per  cent. — the  thigh  and  gluteal  regions  chiefly  :  neck  8-4  per  cent. 
— mostly  posterior  :  head  3-8  per  cent. 

Adenomata. — Of  505  consecutive  cases,  73-6  per  cent,  originated  in 
the  female  breast ;  12-6  per  cent,  in  the  parotid  ;  and  10-3  per  cent,  in 
the  rectum  (polypoid)  ;  other  localities  affected  were  the  submaxillary 
gland,  palate,  sweat-glands,  lachrymal  gland,  septum  nasi  and 
face. 

Papillomata. — Of  386  cases,  the  meatus  urinarius  externus  was  the 
seat  of  the  disease  in  38-8  per  cent.  ;  the  skin — chiefly  of  the  head — in 
26-7  per  cent.  ;  the  external  genitals  (non-venereal)  15-5  per  cent.  ;  the 
bladder  (villous)  5-9  per  cent.  ;  the  tongue  and  mouth  4-9  per  cent.  ; 
the  lips-2  per  cent.  ;  the  rectum  (villous)  1-8  per  cent.  ;  other  seats  affected 
were  the  anus,  trachea  and  conjunctiva. 

Osteomata.—Qt  111  cases,  the  terminal  phalanx  of  the  great  toe 
(subungual)  was  the  seat  of  the  disease  in  30-6  per  cent.  ;  the  femur  in 


390  THE  NATURAL  HISTORY  OF  CANCER 

16-2  per  cent.  ;  the  tibia  in  11-7  per  cent.  ;  multiple  in  9-9  per  cent.  ;  the 
humerus  in  9  per  cent. ;  the  vertebrae  in  4-5  per  cent.  ;  the  other  parts 
affected  being  the  superior  maxilla,  mastoid  process,  scapula,  fifth 
raetacarpal  bone,  innominate,  ulna,  external  auditory  process,  meta- 
tarsal  bone,  terminal  phalanx  of  middle  toe  (subungual — 1  case).  The 
very  frequent  occurrence  of  the  subungual  exostosis  of  the  great  toe, 
and  the  constancy  of  its  attachment  to  the  tibial  side  thereof,  is  remark- 
able. 

Chvndromata. — Of  72  cases,  37-5  per  cent,  were  located  in  the  parotid  ; 
22-2  per  cent,  in  the  hand  ;  22-2  per  cent,  in  the  long  bones  ;  2-8  per  cent, 
in  the  superior  maxilla ;  2-8  per  cent,  in  the  submaxillary  gland ;  the 
other  situations  affected  being  inferior  maxilla,  female  breast,  testis, 
ischio-rectal  region,  lachrymal  gland,  toe,  scapula,  external  ear,  and 
mediastinum. 

Angiomata. — Of  94  cases,  55-3  per  cent,  were  located  on  the  head ; 
21-3  per  cent,  on  the  trunk  ;  7-5  per  cent,  on  the  neck  ;  5-3  per  cent,  on 
the  external  genitals  ;  5-3  per  cent,  on  the  lower  limb  ;  and  5-3  per  cent, 
on  the  upper  limb. 

Cysts. 

In  the  distribution  of  cysts,  the  most  striking  features  are  the  great 
proclivity  to  this  kind  of  formation  of  the  ovary,  and  the  sebaceous  glands 
of  the  skin,  especially  of  the  scalp. 

Of  1,640  cysts,  91-8  per  cent,  were  of  post-natal,  and  8-2  per  cent,  of 
pre-natal  development. 

Of  the  former  group,  48  per  cent,  were  ovarian  or  broad  ligament  cysts. 
(Of  216  cysts  of  this  kind,  84-5  per  cent,  originated  in  the  ovary,  and 
11-5  per  cent,  in  the  broad  ligament).  Sebaceous  cysts  (two-thirds  of 
the  scalp)  amounted  to  29-2  per  cent. ;  spermatic  cord  and  round  ligament 
cysts  5-2  per  cent.  ;  female  breast  4-1  per  cent.  ;  external  genitals  4  per 
cent. ;  dental  (alveolar)  1-9  per  cent. ;  testis  1-5  per  cent.  ;  floor  of  mouth 
1-4  per  cent. ;  and  thyroid  1  per  cent. 

Other  localities  thus  affected  were — peri-articular,  neck,  parotid,  thigh, 
kidney,  omentum,  cerebellum,  uterus,  pelvis,  groin,  retro-peritoneal,  lip, 
loin,  liver,  humerus  and  ringer. 

Of  the  congenital  cysts,  92-3  per  cent,  were  dermoids  :  these  were 
situated  as  follows  : — Head,  41-6  per  cent,  (more  than  half  in  the  orbital 
region)  ;  ovary,  35  per  cent. ;  neck,  17-3  per  cent. ;  other  situations  involved 
being  the  thigh,  scrotum,  sternum,  and  peritoneum. 

Summary. 

In  order  to  show  the  influence  of  locality  in  determining  the  genesis, 
structure,  qualities  and  relative  frequency  of  the  different  kinds  of 
tumours,  I  have  compiled  the  following  tables,  which  are  based  upon  the 
hospital  data  previously  referred  to. 


THE  INITIAL  SEATS  OF  TUMOURS 


391 


TABLE  IX. 

SHOWING  THE  RELATIVE  FREQUENCY  OF  TUMOURS  IN  GENERAL,  AS 
COMPARED  WITH  THAT  OF  THE  CHIEF  LOCAL  VARIETIES,  IN  PERSONS 
OF  THE  TWO  SEXES  COMBINED. 


Kind  of 
Neoplasm. 

Neo- 
plasms in 
General. 

Digestive 
System. 

Stomach. 

Skin. 

Tongue 
and 
Mouth. 

Rectum. 

Lower 
Lip. 

Per  Cent. 

Per  Cent. 

Per  Cent, 

Per  Cent. 

Per  Cent. 

Per  Cent. 

Per  Cent. 

Epithelioma  .  . 

54"5 

93'2 

100 

42-7 

91-36 

85-87 

94-32 

Sarcoma 

9'4 

1-6 



T3 

1-70 

1'50 

T13 

Non-malignant 

neoplasms  .  . 

24-7 

4'0 



12'4 

3'87 

12-63 

4-26 

Cysts 

1T4 

T2 

— 

33'6 

3'07 

— 

0-29 

TABLE  X. 

SHOWING  THE  RELATIVE  FREQUENCY  OF  TUMOURS  IN^GENERAL  IN 
PERSONS  OF  THE  FEMALE  SEX,  AS  COMPARED  WITH  THAT  OF  THE 
CHIEF  LOCAL  VARIETIES  IN  FEMALES. 


Kind  of 
Neoplasm. 

Female 
Neo- 
plasms in 
General. 

Digestive 
System. 

Uterine 
Neo- 
plasms. 

Breast 
Neo- 
plasms. 

Tongue 
and 
Mouth. 

Skin 
Neo- 
plasms in 
Females. 

Ovarian 
Neo- 
plasms. 

Per  Cent. 

Per  Cent. 

Per  Cent. 

Per  Cent. 

Per  Cent. 

Per  Cent. 

Per  Cent. 

Epithelioma  .  . 

48'7 

87'4 

59-30 

77'7 

67'79 

34-1 

3'36 

Sarcoma 

6'3 

2'3 

0'08 

3'9 

6'04 

1-8 

2-96 

Non-malignant 

neoplasms  .  . 

33-4 

7'3 

40-54 

15'7 

12-75 

29-1 

0-12 

Cysts 

11-6 

3'0 

0'08 

2-7 

13-42 

35-0 

93-54     | 

TABLE  XL 

SHOWING  THE  RELATIVE  FREQUENCY  OF  TUMOURS  IN  GENERAL  IN 
PERSONS  OF  THE  MALE  SEX,  AS  COMPARED  WITH  THAT  OF  THE  CHIEF 
LOCAL  VARIETIES  IN  MALES. 


Kind  of 
Neoplasm. 

Male  Neo- 
plasms. 

Digestive 
System. 

Skin. 

Lower 
Lip. 

Tongue 
and 
Mouth. 

Rectum. 

Testicle. 

Per  Cent. 

Per  Cent. 

Per  Cent. 

Per  Cent. 

Per  Cent. 

?er  Cent. 

Per  Cent. 

Epithelioma  .  . 

55"  1 

95-5 

48-94 

97-03 

96-17 

86-15 

29-04 

Sarcoma 

13-6 

1-4 

0-92 

0'60 

0'82 

2-16 

44-09 

Non-  malignant 

neoplasms  .  . 

22'7 

2-6 

17-47 

2-37 

2-05 

11-69 

1-07 

Cysts 

8'6 

0'5 

32-67 

— 

0-96 

— 

25-80 

These  data  show  that  the  liability  of  the  different  organs  to  evolve 
the  various  tumours  is  extraordinarily  variable.  Thus,  while  in  some 
parts  of  the  body  certain  tumours  hardly  ever  arise,  these  same  parts, 


392  THE  NATURAL  HISTORY  OF  CANCER 

nevertheless,  often  originate  other  tumours,  although  the  latter  are  of 
the  rarest  occurrence  in  yet  other  parts. 

Thus,  the  digestive  system  as  a  whole,  as  well  as  each  of  its  chief 
component  organs  (stomach,  liver,  rectum,  intestines  etc.),  manifests 
extraordinary  proclivity  to  epithelioma  in  both  sexes  ;  while,  as  regards 
sarcoma,  non-malignant  tumours,  and  cysts,  there  is  comparative  im- 
munity. This  fact,  in  conjunction  with  others  of  similar  import,  seems  to 
point  to  the  digestive  system  as  being  in  some  way,  specially  concerned 
in  the  causation  of  epithelial  cancer. 

Although  the  proneness  of  the  uterus  to  epithelioma,  as  compared  witli 
its  proneness  to  other  tumours,  is  above  the  average  for  females  in  general, 
yet  it  is  much  surpassed  in  this  respect  by  the  stomach,  rectum,  mamma 
and  tongue. 

By  way  of  contrast  with  the  foregoing,  it  may  be  pointed  out  that 
the  relative  liability  of  the  skin  to  epithelial  cancer,  is  decidedly  below 
the  average  ;  while  that  of  the  ovaries  is  quite  insignificant. 

In  all  of  the  above-mentioned  organs,  the  proclivity  to  sarcoma  is 
decidedly  below  the  average  ;  although  the  relative  frequency  of  its 
occurrence  inter  se,  presents  considerable  variations. 

In  the  uterus,  stomach,  and  skin,  for  instance,  sarcoma  is  remarkably 
rare.  Whereas,  in  the  female  breast,  ovaries  and  rectum,  rather  more 
cases  are  met  with  ;  but,  of  all  the  organs  included  in  these  tables,  only 
the  testis  manifests  great  relative  proneness  to  sarcoma. 

The  most  striking  feature  in  the  neoplastic  pathogeny  of  the  uterus 
is  not  its  proclivity  to  cancer,  but  its  great  relative  proneness  to  non- 
malignant  tumours  (myoma) ;  with  this,  the  almost  complete  immunity 
of  the  stomach,  intestines  and  ovaries  from  such  tumours,  contrasts 
markedly. 

Indeed,  so  great  is  the  relative  frequency  of  epithelioma  of  the  stomach, 
as  compared  with  its  liability  to  non-malignant  tumours  and  cysts  ; 
that,  for  practical  purposes,  the  very  existence  of  these  latter  may  be 
ignored. 

Again,  while  the  relative  proneness  of  the  uterus,  stomach  and 
intestines  to  originate  cysts  is  infinitesimal ;  yet,  tumours  of  this 
kind  arise  in  the  ovaries,  with  such  preponderating  frequency,  as  to 
reduce  the  ratio  of  all  other  ovarian  tumours  to  insignificant  pro- 
portions. 

In  every  part  of  the  body  where  tumours  arise,  we  meet  with  similar 
phenomena. 

These  extraordinary  differences  in  morbid  proclivity,  are  among  the 
most  remarkable  facts  in  the  whole  range  of  neoplastic  pathogeny ;  and 
no  doubt  the  solution  of  the  problem  of  the  origin  of  tumours,  concentres 
in  them. 


It  seems  to  me  impossible  to  account  for  such  vagaries,  otherwise 
than  as  the  result  of  biological  peculiarities  inherent  in  the  various  tissues 

the  affected  parts;  and  in  their  concomitant  developmental  and 
structural  diversities,  all  of  which  are  ultimately  ascribable  to  functional 
modifications. 

No  doubt  in  every  such  locality  there  must  be  corresponding  morpho- 


THE  INITIAL  SEATS  OF  TUMOURS  393 

logical  changes,  although  the  microscope  has  hitherto  failed  adequately 
to  reveal  them. 

It  is  thus  evident,  that  the  influence  of  locality  in  determining  the  V 
genesis,  structure,  and  qualities  of  tumours,  is  very  great. 

In  concluding  this  chapter,  I  append  tables  giving  details  of  my 
analysis  of  15,481  consecutive  primary  tumours,  as  met  with  in  metro- 
politan hospital  patients,  which  will  I  think  be  useful  for  reference 
purposes. 


394 


THE  NATURAL  HISTORY  OF  CANCER 


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THE  INITIAL  SEATS  OF  TUMOURS 


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396 


THE  NATURAL  HISTORY  OP  CANCER 


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THE  INITIAL  SEATS  OF  TUMOURS 


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398 


THE  NATURAL  HISTORY  OF  CANCER 


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THE  INITIAL  SEATS  OF  TUMOURS 


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CHAPTER  XIX 
THE  MORPHOLOGY  OF  MALIGNANT  TUMOURS 

INASMUCH  as  every  part  of  the  body  is  liable  to  its  own  peculiar  forms  of 
cancerous  growth  ;  and  since  the  diverse  characters  manifested  by  each 
variety,  according  to  its  seat  of  origin,  show  that  the  influence  of  the 
locality  in  determining  the  structure  and  progress  of  the  disease  is  very 
great :  it  is  evident  that  no  study  of  the  life-history  of  neoplastic  pro- 
cesses can  be  complete,  which  ignores  pre-existing  structural  peculiarities. 
We  must  bear  in  mind,  that  tumour-products  are  never  of  such  a 
monstrous  nature,  as  not  to  present  some  analogy  with  the  normal 
structure  of  the  part  whence  they  may  originate,  either  in  its  embryonic 
or  post-embryonic  state.  It  is  to  be  regretted  that  modern  pathologists, 
in  their  eager  pursuit  of  microbes  and  specific  causative  agents,  have  so 
far  neglected  this  important  consideration  ;  that  the  links  connecting 
these  extremes  have,  for  the  most  part,  still  to  be  ascertained. 


The  Primary  Tumour. 

:  In  a  previous  chapter,1 1  have  adduced  facts  to  prove  that  the  matrix 
of  a  malignant  tumour  is  generally  a  redundant  formation  of  pre-natal 
origin,  structurally  and  functionally  uncombined  with  the  part  of  the 
body  in  which  it  exists,  although  generally  a  remote  derivative  thereof. 
In  this  respect,  malignant  and  non-malignant  tumours  are  similarly 
conditioned  ;  that  is  to  say,  their  matrix  is  usually  the  outcome  of  vitium 
primce  formationis. 

There  are,  however,  reasons  for  believing,2  that  malignant  and 
other  tumours  may  exceptionally  arise  from  a  matrix  of  post-natal 
origin,  owing  to  the  detachment  of  proliferous  tissue  elements,  in  con- 
sequence of  injury  or  disease.  In  the  latter,  as  in  the  former  case,  however, 
the  tumour  matrix  is  separate  and  distinct  from  the  local  tissues,  in 
which  it  is  embedded. 

The  initial  lesion  of  cancer  is  generally  solitary  ;  and,  so  exceedingly 
minute,  that  its  original  germ  is  probably  but  a  single  one  of  the  con- 
stituent cells  of  the  matrix,  or  a  small  cellular  group. 

This  supposition  accords  with  what  we  know  as  to  the  origin  of 
secondary  cancers  ;  for,  the  capillaries  through  which  the  germs  of  such 
tumours  must  have  passed  are  often  so  minute,  as  not  to  admit  of  the 
passage  of  more  than  a  single  cell.  Thus,  the  primordial  starting-point 

1  Chapter  VII.  2  chapter  XI. 

400 


THE  MORPHOLOGY  OF  MALIGNANT  TUMOURS          401 

of  every  tumour,  as  of  every  organ  of  the  body,  is  in  all  probability  a  X 
single  cell. 

In  its  growth,  as  in  its  genesis,  the  cancerous  new  formation  also 
mimics  the  corresponding  normal  structure  whence  its  matrix  was 
originally  derived  ;  although  it  never  attains  to  the  structural  or  func- 
tional perfection  of  the  physiological  prototype.  The  cancerous  growth 
is,  in  fact,  the  result  of  a  modified,  superinduced  repetition  of  a  certain 
portion  of  the  ontogeny  of  this  prototype.  As  Broca  has  well  said  : 
"  Dans  1'ensemble  c'est  un  exces  de  formation  ;  dans  les  details  c'estVs 
un  arret  de  developpement." 

In  the  case  of  non-malignant  tumours  this  mimicry  is  generally  so 
complete,  that  the  tumour  structure  is  commonly  an  almost  exact  replica 
of  its  physiological  prototype  ;  indeed,  certain  tumours  of  this  kind1 
can  hardly  be  distinguished  from  anomalies  per  excessum. 

Between  these  extremes,  we  meet  with  numerous  intermediate 
forms. 

In  consequence  of  this  peculiarity,  the  anatomical  features  of 
malignant  tumours  are  very  varied,  according  to  the  nature  of  the 
matrix  whence  they  originate  ;  in  this  way,  the  differences  between 
malignant  epithelial  and  connective-tissue  tumours  may  be  explained  ; 
as  also  the  diverse  structural  varieties  of  tumours,  comprised  within 
the  limits  of  each  of  these  types. 

Thus,  malignant  tumours  of  epithelial  origin  increase  in  size,  by  the 
growth  of  solid  bud-like  processes  of  proliferous  epithelial  cells  ;  which, 
as  they  augment,  grow  and  ramify  in  the  adjacent  tissues,  mimicking  the 
ontogenesis  of  their  physiological  prototype.  By  the  repetition  and 
centrifugal  extension  of  this  process,  the  cancerous  tumour  is  formed  ; 
and  this  crude  growth  tends  to  reproduce  itself  indefinitely. 

Along  with  it,  however,  there  also  goes  a  certain  amount  of  organiza- 
tion of  the  growing  mass,  with  manifest  tendency  to  reproduce  struc- 
tural features  characteristic  of  the  physiological  prototype  ;  hence  the 
very  marked  morphological  difference  between  cancers  of  various  parts. 
What,  for  instance,  can  be  more  divergent  in  this  respect,  than  the 
morphological  appearances  of  representative  cancers  from  such  different 
parts  as  the  skin,  stomach,  rectum,  uterus  and  breast  ?2 

The  microscopical  examination  of  such  tumours  shows,  that  they  are 
sufficiently  organized  to  present  unmistakable  histological  resemblance, 
to  the  structures  whence  they  originate.  And  with  this  morphological 
differentiation  certain  corresponding,  but  less  obvious,  physiological 
diversities  may  also  be  detected,  as  I  have  previously  mentioned. 

Herein  malignant  tumours  differ  from  inflammatory  pseudo-plasms, 
which  everywhere  tend  to  reproduce  the  same  granulomatous  structure. 

Although  we  know  from  histology  the  infiltrating  character  of  such 
growths,  yet,  to  the  unaided  senses,  these  tumours  generally  present  as 
more  or  less  circumscribed  masses.  On  careful  examination  of  their 

1  E.g.,  Angiomata,  moles,  lipomata,  subungual  exostcne},  etc.  (q.v.  an  essay  by  the 
author  in  Bristol  Medico-Chirurgical  Journal,  March,  1904,  p.  17). 

2  For  histological  details  reference  may  be  made  to  the  author's  previous  publications — 
viz.,  "  Diseases  of  the  Breast,"  p.  151  et  seq.  ;  "  Uterine  Tumours,"  pp.  31  and  199  ;  also 
"  Twentieth -Century  Practice  of  Medicine,"  vol.  xvii.,  pp.  310,  486,  etc. 

26 


402  THE  NATURAL  HISTORY  OF  CANCER 

periphery,  it  will  be  seen  that  the  passage  from  the  diseased  to  the 
healthy  tissue  is  by  no  means  sharply  denned,  the  irregularly  growing 
edge  of  the  cancer  dovetailing,  as  it  were,  into  the  surrounding  pre- 
existing tissues. 

Of  all  malignant  tumours,  the  sarcomas  are  the  most  circumscribed, 
some  forms  having  a  pseudo-capsule ;  yet,  notwithstanding  this,  pro- 
cesses of  the  disease  nearly  always  spread  out  into  the  surrounding 
tissues,  far  beyond  the  apparent  limits  of  the  tumour. 

Taken  in  their  entirety,  the  cancerous  cells  form  branching,  racemose 
masses,  ingrowing  into  the  surrounding  structures. 

By  serial  sections,  after  the  manner  adopted  by  embryologists,  Hauser 
and  others  have  demonstrated,  that  the  appearance  of  closed  alveoli 
full  of  cells,  revealed  by  the  microscopical  examination  of  sections  of 
epitheliomatous  tumours,  is  really  deceptive  ;  the  spaces  which  appear 
to  be  such,  are  really  nothing  more  than  sections  of  branching 
epithelial  ingrowths,  directly  continuous  with  the  rest  of  the  tumour 
parenchyma. 

The  effect  of  cancerous  growths  on  the  tissues  in  the  midst  of  which 
they  evolve,  is  to  cause  their  destruction  by  "  pressure  atrophy  ";  if, 
indeed,  such  a  term  can  properly  be  applied  to  a  process,  which  is  prob- 
ably due  to  a  special  kind  of  metabolism,  such  as  is  often  seen  in  various 
phases  of  ontogeny. 

If  we  examine  the  growing  edge  of  a  cancerous  tumour,  we  shall 
find  that  the  disease  progresses  by  the  continuous  centrifugal  extension 
of  its  ingrowing  epithelial  processes.  These  spread  most  rapidly  in  the 
directions  of  least  resistance,  which  are  usually  the  adjacent  lymphatics, 
peri-vascular  sheaths  and  small  veins.  As  these  become  distended  with 
cancer  cells,  fine,  elongated,  cord-like  processes  of  cancerous  growth  are 
formed,  which  often  extend  from  the  parent  tumour  far  into  the  sur- 
rounding tissues.  In  this  connexion  nodular  growths  may  develop 
which,  to  the  naked  eye,  appear  to  have  no  connexion  with  the  primary 
tumour.  In  their  subsequent  progress,  these  secondary  formations 
behave  exactly  as  the  primary  growth.  Thus,  as  the  disease  extends, 
the  parent  tumour  blends  with  the  outlying  nodules,  forming  a  diffused 
mass  of  infiltrating  growth. 

In  referring  to  this  infiltrating  characteristic  of  cancer,  Astley  Cooper  1 
says,  when  describing  mammary  cancer  : — "  I  would  observe  that  the 
scirrhous  tumour  is  not  all  of  the  disease  ;  there  are  roots  which  extend 
to  a  considerable  distance  ;  and  those  who  gave  the  disease  the  name  of 
"  cancer,"  probably  knew  more  of  its  nature  than  we  are  disposed  to 
give  them  credit  for.  It  is  supposed  by  some,  that  this  name  was  given 
on  account  of  the  appearance  of  the  surrounding  veins.  I  should  rather 
say  it  was  from  the  appearances  on  dissection,  than  from  anything 
without.  When  you  dissect  a  scirrhous  tumour,  you  see  a  number  of 
roots  proceeding  to  a  considerable  distance  ;  and,  if  you  remove  the 
tumour  only,  and  not  the  roots,  there  will  be  little  advantage  from  the 
operation  :  no  glandular  structure,  nor  any  of  the  roots,  should  be  allowed 
to  remain." 

1  "Lectures  on  Surgery,"  1839,  p'.  386. 


THE  MORPHOLOGY  OF  MALIGNANT  TUMOURS          403 

This  admirable  summary  of  the  subject,  is  entirely  in  accord  with  the 
results  of  modern  research. 

It  will  be  gathered  from  what  has  been  stated,  that  the  integration 
of  cancerous  growths  is  very  inferior  to  that  of  normal  parts.  New 
centres  of  development  are  constantly  arising  among  their  constituent 
proliferating  cells  ;  so  that,  before  the  initial  growth  has  made  much 
progress,  numerous  subsidiary  centres  of  morbid  activity  have  arisen  in 
it,  or  in  its  vicinity. 

The  physical  characters  of  cancerous  tumours  are  determined  by  the 
structure  of  the  part  wherein  they  originate ;  hence,  hard  cancers 
("  scirrhous")  are  the  dominant  forms  that  arise  from  parts  rich  in 
fibrous  tissue,  such  as  the  mamma  and  skin  •;  while,  in  the  uterus,  stomach 
and  rectum,  where  fibrillar  tissue  is  scanty,  soft,  succulent  or  fragile 
forms  of  cancer  predominate. 

The  shape  and  size  of  the  constituent  cells  of  cancerous  tumours,  and 
their  grouping,  vary  according  to  the  locality ;  but  some  resemblance  is 
always  noticeable,  in  these  respects,  between  the  pathological  new 
formation  and  its  physiological  prototype. 

Thus  Johannes  Miiller,1  more  than  half  a  century  ago,  demonstrated 
the  presence  of  casein  in  breast  cancers  ;  and  the  abundance  of  fatty 
matters,  contained  in  the  cells  of  such  neoplasms,  is  well  known.  We 
are  thus  reminded  of  the  similar  metamorphoses,  that  the  cells  of  the 
normal  gland  undergo  during  lactation  ;  but,  the  nearest  approach  to 
normal  secretion  that  the  pathological  structure  ever  produces,  is  a 
scanty,  mucoid  fluid,  not  unlike  a  very  poor  kind  of  colostrum. 

In  comparatively  recent  times,  Waring2  has  demonstrated  the 
important  fact,  that  the  constituent  cells  of  cancers  of  the  stomach  and 
pancreas,  produce  the  same  ferments — pepsin,  trypsin  etc. — as  the 
normal  secretory  cells  of  these  organs. 

If,  then,  the  secretions  elaborated  by  cancerous  new  formations,  fall 
far  short  of  those  produced  by  their  corresponding  anatomical  proto- 
types, we  may  unhesitatingly  ascribe  this  deficiency  to  the  fact ;  that 
secretory  cells  tend  to  lose  their  normal  functional  aptitudes,  when  in  a 
state  of  active  proliferation,  as  the  experiments  of  Martinotti  and  others 
have  shown. 

The  essential  factor  underlying  the  increase  of  cancerous  tumours 
is,  the  continuous  growth  and  proliferation  of  their  constituent  cellular 
elements.  The  pathological  cells  multiply,  like  their  physiological 
prototypes,  chiefly  by  indirect  nuclear  division  ;  and  the  similarity  extends 
even  to  the  details  of  karyokinesis — equatorial  plates,  achromatic 
spindles  etc.3  Thus,  the  component  cells  of  a  cancerous  tumour,  are  the 
direct  descendants  of  the  primary  neoplastic  cells. 

In  studying  pathological  neoplasia,  much  importance  attaches  to 
the  nucleus  and  nuclear  changes,  for  recent  biological  research  indicates, 

1  "  liber  den  feineren  Bau  und  die  Formen  der  krankhaften  Geschwiilste,"  1838. 

2  Journal  of  Anatomy,  etc.,  October,  1893,  p.  142  :  "  The  Physiological  Characters  of 
Carcinomata." 

3  Cattle  and  others  think,  considering  the  comparatively  sparse  occurrence  of  mitotic 
figures  in  the  actively  growing  zone  of  many  cancers,  that  direct  division  of  the  cells 
(a-mitosis)  is  common  "  (Journal  of  Pathology,  etc.,  February,  1894). 

26—2 


404  THE  NATURAL  HISTORY  OF  CANCER 

that  the  nucleus  is  specially  concerned  in  regulating  the  growth  and 
multiplication  of  cells. 

The  nuclei  of  cancer  cells  are  larger,  richer  in  chromatin,  and  they 
more  frequently  originate  karyokinetic  figures,  than  their  physiological 
prototypes.  More  than  a  single  nucleus  is  commonly  present ;  and  the 
nuclei  often  shed  their  chromatin  into  the  surrounding  protoplasm,  as 
a  sort  of  preliminary  to  division,  whereby  the  so-called  "  giant  cells  " 
of  cancer  arise.  Hypo-  and  hyper-chromatic  conditions  of  the  nucleus 
are  frequently  met  with.1 

Asymmetrical  and  multipolar  mitoses  also  occur  with  undue  fre- 
quency ;  and  the  axis  of  cellular  division  is  often  displaced  from  its  normal 
plane,  as  was  first  pointed  out  by  Fabre-Domergue.  Moreover,  abortive 
mitoses  are  not  uncommon.  Nuclear  fragments  detached  during  mitotic 
changes,  probably  originate  the  "  corps  colorables  "  described  by  Foa 
and  others.  Such  conditions  are  most  marked,  where  the  disease  is  in 
active  progress. 

t         It  was  formerly  thought  that  changes  of  this  kind  were  specially 

'"characteristic  of  cancer ;  but  it  is  now  known  that  similar  conditions  are 

met  with  in  various  inflammatory  processes,  and  even  in  non-malignant 

tumours.     Thus,   although   the   mitoses    of   cancer   are   extraordinarily 

variable,  no  new  types  are  produced. 

In  the  processes  of  repair  and  regeneration  after  wounds,  similar 
changes  are  noticeable  ;  as  well  as  in  the  various  transplantation  experi- 
•^  ments  with  epithelial  tissues,  and  especially  in  Loeb's  cultures  of  epidermis 
in  blood-serum  and  agar,  as  previously  mentioned.2 

Pierallini 3  and  D'Arcy  Power,4  by  means  of  various  forms  of  artificial 
stimulation  (heat,  electricity,  traumata  etc.),  succeeded  in  reproducing 
these  conditions  experimentally ;  while  Galeotti 5  has  shown,  by  treating 
proliferous  cells  with  solutions  of  various  poisons  and  chemical  reagents 
etc.,  that  these  mitotic  irregularities  may  be  artificially  produced  in  this 
way  also. 

Taken  in  their  entirety,  these  deviations  from  the  normal  are  but 
the  morphological  expressions  of  a  high  degree  of  reproductive  activity, 
which  is  an  essential  characteristic  of  cancer  cells. 

This  phenomenon  seems  to  me  to  be  of  the  same  nature — in  ex- 
aggerated degree— as  the  accelerated  proliferation  of  epithelial  cells 
noticeable  in  the  processes  of  repair  and  regeneration.  Just  as  this 
exceeds  the  physiological  rate  of  increase  requisite  to  maintain  the 
normal  status,  so  the  former  exceeds  the  latter  ;  but  I  believe  all  these 
manifestations  belong  to  the  same  order  of  events. 

The  wonderful  reproductive  activity  of  cancer  cells,  enables  us  to 
understand  how  a  single  such  cell,  may  be  the  germ  of  a  large  tumour — 
even  the  largest.  It  is  chiefly  in  this,  their  dynamic  aspect,  that  cancer 
cells  differ  from  normal  cells.  In  their  young"  state,  as  Klebs,  Waldeyer 

1  Hansemann,  Arch.  f.  path.  Anal.,  1890,  Bd.  cxix.,S.  299;  ibid.,  1891,  Bd.  cxxiii., 
TT?7  v   '  j-        mikrosk°Pische  Diagnose  der  bbsartigen  Geschwiilste,"  1902,  S.  91  ,  and 

,eber  die  Anaplasie  der  Geschwiilstzellen,"  etc.,  Arch.  f.  path.  Anat.,  1902,  Bd.  cxxix., 
o.  4do. 

2  Chapter  VIII.  3  LO  Sperimentah,  1.,  p.  37. 
|  British  Medical  Journal,  1893,  vol.  ii.,  p.  830. 

6  Beitr.  z.  path.  Anat.,  etc.,  1893,  Bd.  xiv.,Heft  2,  S.  249  ;  also  1897,  Bd.  xx.,  S.  192. 


THE  MORPHOLOGY  OF  MALIGNANT  TUMOURS          405 

and  others  have  observed,  both  possess  contractile  and  locomotive 
properties. 

Cancer  cells  are  short-lived,  for  they  are  soon  overtaken  and  destroyed 
by  fatty,  caseous,  mucoid,  hyaline  and  other  degenerative  changes  ; 
while  vacuolation  is  of  common  occurrence.  These  and  other  changes 
in  cancer  cells,  have  been  carefully  studied  and  described  by  Pianese,1 
Hansemann  and  others. 

It  will  be  gathered  from  what  has  been  stated,  that  cancer  cells  grow 
and  multiply  more  rapidly  than  their  physiological  congeners  ;  while,  at 
the  same  time,  their  vitality  is  less  stable  and  their  developmental  power 
less  complete. 

With  regard  to  the  occurrence  of  reduction  of  the  nuclear  chromo- 
somes ("  heterotypical  mitosis"),  as  a  special  characteristic  of  cancer 
cells,  this  has  been  disproved  by  the  discovery  of  similar  changes  in 
various  processes  having  nothing  to  do  with  cancer  ;  and  by  the  artificial 
production  of  the  same,  by  chemical  stimulation  etc.,  as  mentioned  in  a 
previous  chapter.2 

In  like  manner,  the  significance  of  the  various  pseudo-parasitic  bodies 
("  endocytes")  found  in  cancer  cells,  and  their  vicinity,  has  been  fully 
explained  in  Chapter  X.  ;  where  reference  was  also  made  to  the  frequent 
presence  in  cancerous  tumours,  of  various  non-specific  microbes. 

Leucocytes  and  red  blood-corpuscles  have  often  been  detected  between 
closely  approximated  cancer  cells,  and  even  within  them  ;  while  the 
invagination  of  one  or  more  cells  within  another,  has  actually  been  seen 
to  occur  by  many  observers. 

These  appearances  have  been  variously  interpreted.  By  some 
pathologists,  as  previously  mentioned,3  they  are  regarded  as  evidence  of 
conjugation,  rejuvenescence,  or  "  maturation "  of  the  tumour  cells ; 
others  have  mistaken  included  cells  of  this  kind  for  "  cancer  parasites  "; 
while  Strobe,  Podwyssotzki  etc.,  maintain  that  they  are  simply  signs 
of  phagocytosis.  It  accords  with  this  last  interpretation,  that  leuco- 
cytes between  and  within  cancer  cells,  are  most  frequently  seen  in 
inflamed  areas.  Under  these  circumstances  mast  cells  are  commonly  met 
with.  Another  notable  feature  is  that  the  stroma  of  the  actively  growing 
zone  of  cancerous  tumours,  is  invariably  infiltrated  with  numerous  small, 
round,  nucleated  cells  ;  and,  as  Goldmann4  has  shown,  its  vascularity 
is  enormously  increased. 

It  has  been  shown  by  Ide  and  others,  that  the  physiological  epithelial 
cells  are  knit  together  and  communicate  freely  with  their  neighbours,  by 
small  bridges  —  ponts  intercellulaires  —  in  which  both  cell  membrane 
and  protoplasm  are  involved,  and  sometimes  even  nuclear  filaments. 
It  is  probable  that  all  the  cells  of  the  body,  are  knit  together  in  this 
way. 

In  malignant  epithelial  tumours,  these  connecting-links  between  the 
different  component  cells,  although  not  invariably  lacking,  are  generally 

1  Ziegler's  Beitr.  z.  path.  Anat.  (supplement),  1896  ;  for  epitome,  vide  Chapter  X.  of 
this  work. 

2  Chapter  IX.  3  Ibid. 

4  Deutsche  med.  Woch.,  1906,  No.  41  ;  also  Lancet,  1907,  vol.  ii.,  p.  1236.  ,       / 


406  THE  NATURAL  HISTORY  OF  CANCER 

very  defective  and  inefficient ;  indeed,  in  many  cancers,  the  constituent 
cells  seem  to  exist  completely  detached  from  one  another,  immersed  in 
an  albuminous  fluid,  which  is  limited  by  the  surrounding  stroma. 

This  want  of  cohesion  between  their  constituent  cells,  is  probably 
one  of  the  chief  reasons  why  cancers  are  so  prone  to  disseminate  ;  and 
it  is  probably  owing  to  conditions  of  this  sort,  that  some  cancers  are  so 
much  more  prone  to  disseminate  than  others. 

In  the  initial  stages  of  their  growth,  malignant  tumours,  like  their 
corresponding  physiological  prototypes,  are  destitute  of  bloodvessels 
and  nerves  ;  it  is  only  at  a  later  period  that  their  deficiencies  in  this  respect 
are  made  good,  by  outgrowths  from  the  surrounding  tissues.  Moreover, 
it  is  noteworthy  that  neither  bloodvessels  nor  nerves  are  found  within 
the  cancer  alveoli,  any  more  than  they  are  within  the  corresponding 
parts  of  the  physiological  prototype. 

Besides  this,  the  relations  of  tumour  and  prototype  to  the  lymphatic 
system  are  very  similar  ;  thus,  as  De  Sinety  has  showTi,  within  the  mem- 
brana  propria  of  the  normal  mammary  acini,  there  exists  an  imperfect 
lining  of  endothelial  cells,  which  is  probably  a  derivative  of  the  lymphatic 
system  ;  and  Cornil  and  Ranvier — by  injection  of  Prussian  blue  and 
nitrate  of  silver  staining — have  demonstrated  that,  in  mammary 
cancer,  the  alveoli  are  in  direct  communication  with  the  lymphatic 
radicles. 

It  is  noteworthy  that  the  endothelial  cells  of  the  latter,  take  no  part 
in  the  cancerous  process. 

From  the  foregoing  we  learn,  that  there  is  nothing  specific  about 
cancer  cells  and  structures,  as  was  formerly  believed  ;  there  is  departure 
from  the  normal  type  of  development,  but  no  foreign  structures  are  pro- 
duced. Thus,  it  is  chiefly  on  account  of  the  greatly  increased  numbers 
of  their  constituent  cells,  of  their  disorderly  grouping,  of  the  comparatively 
imperfect  degree  of  development  attained,  and  of  their  less  stable  vitality, 
that  cancerous  structures  differ  from  their  normal  prototypes. 

This  conformity  is  quite  as  marked  in  the  case  of  the  stroma,  as  in 
the  case  of  the  cancer  cells  ;  for  this  also  takes  after  the  pre-existing 
structure  of  the  affected  part.  It  has  been  much  discussed,  whether 
the  cancer  stroma  is  of  new  formation,  or  simply  the  modified  pre-existing 
structure.  It  seems  certain,  from  various  considerations  ;  but  especially 
from  the  phenomena  presented  by  the  growth  of  secondary  cancers  in 
distant  organs,  and  within  bloodvessels,  that  the  stroma  is  a  new 
formation. 

It  must  be  borne  in  mind  that  the  epithelial  elements  whence  cancers 
originate,  are  normally  in  intimate  contact  with  a  layer  of  immature 
connective  tissue  rich  in  cellular  elements,  which  is  probably  the  source 
of  the  newly  formed  granulation  tissue,  whence  the  cancer  stroma  evolves. 
How  otherwise  can  we  explain  the  fact,  that  the  stroma  of  secondary 
tumours  is  so  like  that  of  the  primary  one  ? 

Ribbert  and  others  who  uphold  the  connective-tissue  origin  of  cancer, 
maintain  that  proliferative  changes  of  this  kind  in  the  sub-epithelial 
connective  tissue,  precede  the  morbid  proliferation  of  the  epithelial 
cells ;  and  constitute,  in  fact,  the  initial  cancerous  change. 


THE  MORPHOLOGY  OF  MALIGNANT  TUMOURS          407 

The  cancer  stroma  is  well  provided  with  various  cellular  constituents 
(fusiform,  stellate,  and  flattened  forms,  as  well  as  lymphocytes,  mast 
cells  and  leucocytes),  in  connexion  with  which  mitotic  figures  may  often 
be  detected. 

Within  the  cancer  stroma,  numerous  small  arteries,  veins  and 
capillaries  ramify.  The  degree  of  vascularity  of  cancer  in  different 
organs  is  very  variable  ;  and,  even  in  different  parts  of  the  same  tumour, 
similar  irregularities  are  met  with.  These  vessels  have  been  injected 
by  Goldmann,1  Thiersch,  Billroth  and  others  ;  and  found  to  form  net- 
works, around  the  sprouting  cancer-cell  complexes.  They  are  generally 
more  numerous  and  less  regular  in  their  calibre  and  arrangement,  than 
the  corresponding  normal  bloodvessels,  tortuous  dilatations  and  small 
sacculations  being  of  frequent  occurrence.  These  lesions  are  occasionally 
so  marked  as  to  produce  a  telangiectasic  condition.  According  to 
Quenu,  the  walls  of  the  vessels  are  often  thickened  and  their  lumina 
occluded,  in  consequence  of  chronic  endarteritis  ;  and  Goldmann  has 
noted  that  degeneration  of  the  vascular  walls  is  a  prominent  feature, 
even  in  early  stages  of  the  disease. 

While  the  vascular  system  of  cancers  can  be  readily  injected  by  the 
arteries — even  the  smallest — it  is  generally  difficult  to  do  so  by  the 
veins,  the  substance  injected  then  finding  its  way  into  the  circum- 
ferential venous  system,  instead  of  into  that  of  the  neoplasm.  This  is 
probably  due  to  the  frequent  blocking  of  the  veins  by  the  growth  of  the 
neoplasm,  by  thrombi  etc.  Thus  may  be  explained  the  venous  engorge- 
ment, that  is  almost  invariably  associated  with  cancer. 

Accompanying  the  stromal  bloodvessels  are  numerous  lymphatics, 
which  have  been  injected,  and  their  distribution  studied  by  Schroder, 
van  der  Kolk,  Krause,  Rindfleisch  and  others.  In  the  case  of  mammary 
epithelial  cancer,  as  previously  mentioned,  their  radicles  are  in  direct 
communication  with  the  alveoli  ;  a  similar  condition  probably  holds  for 
other  forms  of  cancer.  This  enables  us  to  understand,  the  great  frequency 
of  dissemination  in  the  lymphatic  glands. 

Probably  one  reason  why  sarcomas  comparatively  rarely  disseminate 
in  the  lymph-glands,  is  that  but  few  lymphatics  enter  into  their  compo- 
sition ;  indeed,  the  very  existence  of  lymphatics  in  these  tumours  has  been 
denied  by  some  pathologists,  but  Pacinotti  and  others  have  demon- 
strated their  presence. 

Cancers  have  hitherto  generally  been  regarded  as  nerveless ;  but 
vaso-motor  filaments  accompany  the  stromal  bloodvessels,  although  this 
is  denied  by  Verneuil  and  Nepveu.  H.  Young,2  who  has  lately  investi- 
gated this  subject,  found  nerve  filaments  in  all  kinds  of  malignant  tumours, 
the  fibres  being  with  or  without  myeline.  These  nerves  generally  accom- 
panied the  stromal  bloodvessels,  and  appeared  to  be  branches  of  those 
normally  existing  in  the  invaded  tissues. 

The  chemical  analysis  of  cancerous  growths — much  neglected  of  late — 

has  hitherto  failed  to  reveal  the  presence  of  any  specific  morbid  substance. 

Albuminous  constituents  predominate.     Detailed  analyses  may  be  found 

in  the  works  of  Lebert,  Walshe  and  J.  Miiller  ;  but  I  am  not  aware  of  any 

1  Op.  cit.  2  Journal  of  Experimental  Medicine,  1897,  vol.  ii.,  No.  1. 


403  THE  NATURAL  HISTORY  OF  CANCER 

recent  publications  of  this  kind,  other  than  those  I  have  previously 
referred  to. 

It  has  lately  been  shown  that  glycogen  is  invariably  present ;  and, 
according  to  Freund,  so  is  sugar.  Glycogen  is  most  abundant  in  the 
rapidly  growing  forms  of  the  disease.  In  this  respect,  cancer  elements 
resemble  immature  and  rapidly  growing  structures  in  general,  which  are 
^  always  rich  in  glycogen.  Beneke  has  found  an  abundance  of  cholesterin 
and  myelin. 

According  to  recent  observations,  the  juice  of  perfectly  fresh  mammary 
cancers  is  of  an  alkaline  or  neutral  reaction  ;  whereas,  within  a  few  hours 
after  death,  the  reaction  has  become  acid.  In  this  respect  cancer 
resembles  the  physiological  tissues. 

Blumenthal1  and  Bergell2  find  that  cancers  contain  more  albumin 
and  less  globulin  than  other  tissues,  being  particularly  rich  in  nucleo- 
albumin  ;  and  that  cancer  elements  are  specially  susceptible  to  trypsinic 
digestion  etc.  ;  while  Petry3  claims  that  there  is  a  special  intra-cellular 
cancer  ferment — malignin — by  means  of  which  cancers  are  endowed  with 
their  special  qualities.  According  to  Blumenthal,  the  pancreatic  digestion 
of  cancerous  tissues  takes  a  different  course  to  that  of  other  tissues,  being 
"y  arrested  at  the  formation  of  intermediate  chemical  products,  instead  of 
going  on  to  the  usual  terminal  reactions. 

Beard 4  maintains  that  the  albumins  of  cancer  are  dextro-rotatory, 
the  albumins  of  the  normal  body  being  levo-rotatory  ;  but  this  needs 
confirmation. 

Examining  malignant  tumours  for  enzymes,  Petry  found  that  can- 
cerous substances  readily  undergo  autolysis  with  increase  of  non- 
coagulable  proteids,  and  the  formation  of  leucin,  tyrosin,  hexon  and 
purin  bases,  at  the  expense  of  the  most  complex  coagulable  proteids. 
This  autolysis  was  due  to  the  action  of  a  proteolytic  ferment,  the  products 
of  which  corresponded  with  those  found  by  Salkowski,  in  autolysis  of 
normal  tissues. 

It  seems  probable  that  the  tissues  of  malignant  tumours,  like  the 
normal  tissues,  teem  with  enzymes  ;  but  there  is  no  proof  that  their 
specific  quah'ties  are  in  any  way  directly  proportional  to  malignancy. 
Perhaps  the  most  abundant  and  constant  enzyme  met  with  in  cancers 
is  the  amylolitic,  which  is  interesting  when  wre  recollect  the  richness  in 
glycogen  of  these  tumours.  Buxton5  found  in  cancerous  tumours 
/>  proteolytic  enzymes,  amylose,  lipase,  catalase,  peroxidase  and  oxidase  ; 
while  MacFadyean  and  Harden — working  chiefly  with  mammary  cancer 
— found  invertase,  maltase,  amylase,  proteolytic  enzymes,  catalase, 
oxidase,  traces  of  lipase,  and  peroxidase,  but  no  lactose. 

Referring  to  these  results,  Buxton  judiciously  remarks  :  "  The  only 
conclusion  they  seem  to  warrant  is,  that  a  number  of  enzymes  are 
commonly  present  in  cancerous  tumours,  and  that  their  amount  and 
kind  are  independent  of  the  character  or  malignancy  of  the  growths,  and 

1  Berlin.  kUn.  Woch.,  1905,  xliii.,  S.  376. 

Deutsche  med.  Woch.,  etc.,  June  6,  1907. 
*   Zeits.  f.  physiol.  Chemie,  1899,  Bd.  xxvii.,  S.  398. 
•*  New  York  Medical  Record,  October  19,  1907. 

Journal  of  Medical  Research,  1903,  vol.  ix.,  p.  356  ;  also  ibid.,  1905,  vol.  xiii.,  p.  543. 


THE  MORPHOLOGY  OF  MALIGNANT  TUMOURS          409 

- 

are  very  similar  to  those  found  in  the  normal  tissues  of  the  same  part." 
In  short,  it  is  evident  that,  until  we  know  more  about  the  enzymes  of 
the  normal  tissues,  it  is  impossible  to  arrive  at  any  definite  conclusion, 
as  to  the  special  significance  of  the  enzymes  of  cancerous  tumours.1 

Hewlett  and  Brodie  could  find  no  traces  of  albumoses  in  cancerous 
tumours,  although  in  cultures  of  pathogenic  bacteria  such  substances 
abound.  It  should,  however,  be  mentioned  that  Meyer  has  found 
splenic  extracts  from  cancerous  subjects,  of  double  the  toxicity  met  with  ^ 
in  other  cachectic  states  ;  and,  in  disintegrating  cancerous  tissues,  Blu- 
menthal  has  met  with  albumoses.  Brodie  failed  to  find  even  a  trace  of 
either  chitin  or  cellulose  in  cancerous  tumours,  which  indicates  the 
absence  of  encapsuled  protozoa. 

Hewlett's  investigations  2  show  that  the  cells  of  epithelioma,  sarcoma 
and  adenoma,  contain  about  the  same  amount  of  phosphorus,  as  those 
of  the  normal  tissues  ;  that  there  is  no  special  distribution  of  iron  in  these 
tumours,  their  cells  being  neither  richer  nor  poorer  in  this  respect,  than 
the  ordinary  tissue  cells;  and  that  the  proteids  of  cancer, like  those  of  other 
cellular  organs,  consist  chiefly  of  nucleo- albumin. 

Reference  has  previously  been  made  to  Waring's  important  researches, 
on  the  physiological  properties  of  carcinomata. 

As  I  have  specially  indicated  in  a  previous  chapter,3  the  presence  of 
various  heterotopic  structures  (e.g.,  bone,  cartilage,  striped  muscle  etc.) 
in  malignant  tumours  is  an  event  of  great  interest,  as  indicating  genetic 
connexion  with  pre-natal  developmental  irregularities  (vitium  primoe 
formationis). 

Although  the  matrix  of  a  cancerous  tumour  is  not  integrated  with 
the  tissues  of  the  part  in  which  it  is  embedded,  yet  it  cannot  usually  be 
regarded  as  a  heterotopic  structure,  since  it  is  but  a  pre-natal  derivative 
of  the  locality  :  consequently  there  is  always  some  resemblance  between 
such  tumours  and  local  structure. 

It  not  uncommonly  happens,  however,  that  the  matrix  of  a  cancerous 
tumour  at  the  time  of  its  genesis,  is  displaced  from  its  original  habitat  ; 
and  then  we  get  a  truly  heterotopic  cancer.  Tumours  of  this  type  form 
a  very  interesting  group,  which  ought  to  be  more  carefully  studied,  than 
they  hitherto  have  been  ;  for  they  throw  a  strong  light  on  tumour 
pathogenesis. 

For  instance,  there  are  on  record  many  examples  of  malignant 
epithelial  tumours  arising  in  bones,  lymph-glands  and  other  localities, 
where  epithelial  elements  are  normally  absent.  Thus,  Councilman 
found  a  nodule  of  cutaneous  epidermoidal  cancer,  embedded  in  the 
osseous  substance  of  the  sternum  :  to  account  for  this,  we  must  remember 
that  the  sternum  is  evolved  by  the  gradual  approximation  and  fusion  of 
twyo  lateral  halves  ;  in  this  process,  offsets  of  the  overlying  cutaneous 
matrix  may  be  entangled  and  sequestrated  ;  that  this  actually  happens 
we  know  from  the  occurrence  of  dermoid  cysts  in  this  bone  and  its 
vicinity  ;  the  tumour  described  by  Councilman,  no  doubt  sprang  from 

1  For  further  reference  to  this  subject,  vide  Chapter  IX. 

2  British  Medical  Journal,  1894,  vol.  ii.,  p.  190  ;  ibid.,  1895,  vol.  ii.,  p.  206. 

3  Chapter  VII. 


410  THE  NATURAL  HISTORY  OF  CANCER 

one  of  these  cutaneous  "  rests,"  which  had  been  embedded  in  the  sub- 
stance of  the  bone. 

In  like  manner,  we  see  mammary  epitheliomas  and  sarcomas,  arising 
in  the  axilla,  quite  independently  of  the  mammary  gland,  from  mammary 
"  rests  "  of  pre-natal  origin,  of  which  I  know  of  many  examples  ;  and 
the  origin  of  epidermoidal  cancers,  from  the  mucosa  of  the  corpus  uteri, 
is  of  similar  import. 

In  many  parts  of  the  body,  such  as  the  buccal  cavity,  the  outbreak 
of  cancer  is  commonly  preceded  by  obvious  hyperplastic  changes  (leuco- 
plasia)  in  the  surface  epithelia.  Moreover,  it  is  noticeable  that  these 
lesions  are  seldom  limited  to  the  precise  starting-point  of  the  cancerous 
disease.  This  clearly  implies  that  the  abnormal  activity,  which  at  a 
given  spot  culminates  in  cancer,  affects  in  a  less  degree  the  adjacent 
epithelia  of  the  region  for  a  considerable  extent.  Lesions  of  this  type 
are  commonly,  but  very  erroneously,  regarded  as  "  inflammatory  "  in 
origin,  that  is  to  say,  as  the  outcome  of  extrinsic  causes  ;  whereas,  my 
belief  is,  that  these  morbid  conditions  are  the  result  of  proliferative 
hyperplasia  of  intrinsic  origin,  in  which  altered  metabolism  of  the  local 
cells  plays  the  chief  part.  The  question  occurs  whether  all  parts  of  the 
body,  in  which  cancers  arise,  are  not  similarly  circumstanced.  The 
indications  at  present  forthcoming  are  decidedly  in  favour  of  an  affirm- 
ative answer  ;  the  admirable  researches  of  Heidenhain 1  have,  at  any 
rate,  answered  the  question  in  this  sense  for  the  female  breast.  He  has 
conclusively  shown  that  every  mamma  containing  a  cancerous  tumour, 
is  diseased  throughout.  Its  secretory  cells  are  unduly  numerous,  and 
they  everywhere  show  signs  of  excessive  proliferative  activity  ;  while, 
the  peri-acinous  connective  tissue  is  much  increased,  its  nuclei  are  unduly 
abundant,  and  it  is  infiltrated  with  small  round  cells.  Parts  in  such  a 
condition,  are  evidently  more  prone  to  originate  cancer,  than  perfectly 
normal  structures. 

Changes  of  this  kind  indicate  regional,  as  well  as  local  structural 
proclivity. 

Local  Dissemination. 

As  previously  mentioned,  at  a  comparatively  early  stage  of  the 
disease,  there  may  usually  be  found  in  the  vicinity  of  the  primary  tumour, 
or  even  at  some  distance  from  it,  small  satellite  nodules,  which  are  the 
first  obvious  signs  of  local  dissemination. 

Careful  histological  examination  of  these  nodules  and  their  con- 
nexions by  serial  sections  etc.  shows  that,  as  a  rule,  they  are  directly 
continuous  with  the  parent  tumour  by  means  of  cord-like  processes  of 
cancerous  growth,  which  spread  by  way  of  the  adjacent  lymphatics  and 
small  veins.  It  is  noticeable,  as  Seelig,  Hoggan  and  other  histological 
investigators  of  this  matter  have  specially  pointed  out,  that  the  endo- 
thelial  cells  of  the  intima  take  no  part  in  the  morbid  process  ;  and,  for 
a  considerable  time,  maintain  their  integrity,  in  spite  of  this  invasion. 

There  are  good  reasons  for  believing  that  the  local  dissemination  of 
cancer  is  chiefly  effected  in  this  way,  that  is  to  say,  by  the  continuous 
1  Arch.  I  klin.  Chir.,  1889,  Bd.  xxxix.,  S.  97. 


THE  MORPHOLOGY  OP  MALIGNANT  TUMOURS          411 

centrifugal  extension  of  ingrowing  cancerous  processes,  or  by  "  per- 
meation," as  Handley  calls  it. 

As  I  showed  many  years  ago,1  the  disease  often  spreads  in  this  manner 
to  localities  at  a  considerable  distance  from  the  primary  tumour,  e.g.  in 
cancer  of  the  breast,  the  mediastinal  tissues,  pleurae  and  intra-thoracic 
organs  may  be  thus  invaded  ;  and,  in  like  manner,  the  disease  may  be 
conveyed  from  one  breast  to  the  other,  to  the  upper  end  of  the  humeras, 
sternum  etc. 

Since  each  of  these  local  dissemination  nodules  constitutes  a  fresh 
centre  of  the  disease,  which  progresses  like  the  parent  tumour,  it  is 
obvious  that- cancer  may  be  widely  disseminated  by  "  permeation." 

Billroth  seems  to  have  had  an  inkling  of  this,  for  he  long  ago  wrote, 
with  regard  to  the  dissemination  of  mammary  cancer  in  the  liver  :  "  My 
idea  is  that  the  cancerous  material  is  directly  transported  through  the 
lymphatics  of  the  mediastinum,  diaphragm  and  suspensory  ligament  of 
the  latter."2 

There  can  be  no  doubt  that  this  continuous  centrifugal  spread  of  the 
disease  by  direct  extension,  is  greatly  favoured  by  the  many  direct 
communications  between  the  lymphatic  and  venous  radicles  to  which 
Leaf  3  has  lately  called  attention,  for  the  venous  route  is  as  important 
for  "  permeation,"  as  the  lymphatic  route. 

While,  however,  conceding,  as  I  always  have,  the  paramount  import- 
ance of  this  method  for  local  dissemination,  I  am  unable  to  support 
Handley  4  in  his  contention,  that  "  permeation  "  is  the  alpha  and  omega 
of  dissemination  in  general. 

In  addition  to  this  method  of  direct  extension,  I  think  we  must  also 
recognize  the  fact,  that  cancer  is  often  spread  by  the  conveyance  of 
cancer  cells — detached  from  the  primary  tumour  or  its  satellite  offshoots — 
by  the  lymph  and  blood  streams.  Thus  those  really  discontinuous, 
satellite  nodules  arise,  which  may  constantly  be  found  in  the  persons  of 
those  suffering  from  disseminated  cancer. 

In  effecting  detachment  from  the  parent  tumour,  and  in  the  sub- 
sequent course  of  their  migration,  especially  in  its  early  stages,  dissemina- 
tion is  greatly  aided  by  the  spontaneous  movements  of  the  cancer  cells, 
of  which  I  have  previously  made  mention. 

This  subject  can  be  more  satisfactorily  investigated  in  the  uterus, 
than  in  the  mamma  and  most  other  organs  ;  gynaecological  pathologists 
(Hofmeier,  Winter,  Seelig  and  others)  have  reported  and  carefully 
studied,  many  striking  examples  of  the  discontinuous  dissemination  of 
cancer  in  this  organ.  Thus,  in  a  considerable  number  of  instances, 
primary  cancer  of  the  cervix  uteri  has  been  found  concomitant  with 
secondary  cancerous  foci  of  the  same  structure  in  the  corpus,  without 
there  being  any  morbid  alteration  of  the  intervening  parts  ;  and,  in  a  few 
cases,  with  the  primary  cancer  in  the  corpus,  secondary  nodules  have 

1  "  Diseases  of  the  Breast,"  1894,  chap.  ix. 

2  In  like  manner  Astley  Cooper,  whose  knowledge  of  the  anatomy  and  pathology 
of  the  breast  was  far  in  advance  of  his  time,  wrote  :  "  The  internal    thoracic  absorbents 
carry  the  diseased  matter  to  the  liver,  which  becomes  tuberculated,  and  assumes  the  true 
scirrhous  character  "  ("  Lectures  on  Surgery,"  1839,  p.  376). 

3  Lancet,  1900,  vol.  i.,  p.  607.  *  Ibid.,  1905,  vol.  i.,  pp.  909,  983,  and  1047. 


412  THE  NATURAL  HISTORY  OF  CANCER 

been  found  in  the  cervix  or  portio.  In  all  these  cases,  the  most  careful 
histological  examination  failed  to  reveal  any  direct  continuity,  between 
the  primary  and  secondary  tumours.  Referring  to  such  cases,  Seelig 
says  that  the  communication  between  the  lymphatics  of  the  cervix  and 
corpus,  is  very  much  freer  through  the  numerous  large  branches  within 
the  musculature,  than  it  is  through  the  much  smaller  branches  uniting 
the  mucosa  of  the  two  uterine  segments  ;  and  he  finds  that  in  such  cases 
as  those  we  are  now  discussing,  the  disease  disseminates  along  these  lines. 

Many  similar  instances  have  been  reported  in  the  mamma,  and  other 
parts  of  the  body. 

I  shall  subsequently  have  to  refer  to  the  facts  relating  to  intra- 
vascular  cancers,  cancer  emboli,  and  the  presence  of  free  cancer  cells 
in  the  blood,  which  support  this  contention  ;  as  also  to  some  other 
facts  of  similar  import,  concerning  dissemination  in  lymph-glands  and  in 
distant  parts. 

The  local  dissemination  of  cancer,  varies  much  in  different  parts, 
in  respect  to  date  of  onset,  direction,  and  extent ;  and,  in  the  epithelial 
type  of  the  disease,  this  form  of  dissemination  is  of  more  frequent  occur- 
rence, than  in  the  connective-tissue  type. 

Thus,  there  is  great  difference  as  regards  proclivity  to  local  dis- 
semination, between  cancer  of  the  breast,  uterus,  tongue,  and  "  rodent  " 
cancer  of  the  skin  ;  between  periosteal  sarcoma  of  the  bones,  the  myeloid 
form  of  sarcoma,  glioma  etc. 

Local  dissemination  has  an  important  bearing,  when  the  question  of 
operation  is  under  consideration  ;  for,  it  appears  from  the  following 
considerations,  that  the  spread  of  the  disease  to  the  lymphatic  glands 
and  to  the  system  generally,  is  greatly  favoured  by  local  dissemination. 
Thus,  of  192  cases  with  local  dissemination,  Torok  and  Wittelshofer 
found  the  lymphatic  glands  invaded  in  52-6  per  cent.,  and  metastases 
in  72-9  per  cent.  ;  whereas,  of  174  cases  free  from  local  dissemination, 
the  lymphatic  glands  were  affected  only  in  42-5  per  cent.,  and  there 
were  metastases  in  but  45-4  per  cent. 


Lymph-Gland  Dissemination. 

One  of  the  earliest  consequences  of  the  development  of  a  cancerous 
tumour  is,  that  the  adjacent  lymph-glands  become  enlarged.  This 
condition  may  be  only  transitory,  as  in  the  glandular  enlargements 
occasionally  seen  in  the  course  of  most  infectious  diseases,  in  association 
with  certain  non-malignant  tumours,  and  in  the  glands  left  behind  after 
extirpation  of  a  cancerous  part.  Such  enlargements  are  usually  ascribed 
to  "  irritation,"  or  "  chronic  inflammation." 

Histological  examination  reveals  nothing  more  than  undue  increase 

in  number  and  size  of  the  lymphoid  cells,  together  with  thickening  of 

the  fibrous  reticulum,  and  proliferation  of  its  nuclei,  as  well  as  hyper- 

plasia  of  the  endothelia.     These  changes  cause  obstruction  of  the  lymph- 

^sinuses  ;  and  consequent  clogging  of  the  circulation  through  the  gland. 

When  associated  with  cancer,  this  glandular  enlargement  is  usually 


THE  MORPHOLOGY  OF  MALIGNANT  TUMOURS          413 

followed,  after  a  time,  by  the  development  in  the  affected  glands  of 
cancerous  growths,  similar  in  character  and  structure  to  the  primary 
neoplasm.  This  indicates  that  the  secondary  growths  are  derivatives 
of  the  primary  one.  Yet  it  is  exceptional  to  find  any  direct  continuity 
between  the  two.  Wherein,  then,  does  the  connexion  consist  ?  As 
I  have  previously  mentioned,  the  cellular  elements  of  malignant  epithelial 
tumours,  like  their  corresponding  physiological  prototypes,  are  very 
closely  related  to  the  lymph  radicles.  Hence  detached  cellular  elements 
from  the  tumour,  readily  enter  the  lymphatics,  where  they  have 
been  seen  and  studied  by  Langhans,  Waldeyer,  Leopold,  Seelig  and 
others.  No  doubt  this  disconnexion  of  the  cancerous  cell  from  its  normal 
nexus,  and  its  transportation  into  the  lymph-radicles,  is  effected  largely 
by  its  own  contractile  and  motor  properties  ;  which,  as  Klebs,  Waldeyer 
and  others  have  shown,  are  considerable — especially  in  its  young  state. 
The  migration  of  leucocytes  from  the  bloodvessels  into  the  lymphatics, 
is  a  similar  phenomenon,  which  has  been  demonstrated  by  Thoma  in  all 
its  stages  (1873). 

But  these  considerations  must  not  blind  us  to  the  fact  that,  even 
in  the  absence  of  any  such  active  participation,  cancer  cells  may 
nevertheless  be  transported  into  the  lymphatics  and  carried  by  them 
into  the  adjacent  lymph-glands,  just  as  happens  with  the  granular 
matter  introduced  in  tattooing,  with  anthracite  particles  absorbed  from 
the  lungs  of  colliers  and  deposited  in  the  bronchial  glands  etc.  In  the 
dissemination  of  cancer,  besides  the  living  cancer  cells,  no  doubt  many 
moribund,  disintegrating  cellular  elements,  and  much  granular  detritus 
therefrom,  as  well  as  epiphytic  microbes,  are  constantly  being  carried 
in  one  or  other  of  these  ways  into  the  lymphatic  glands.  From  the 
smallness  of  the  lymph-radicles,  it  may  be  inferred  that  such  transported 
fragments  must  be  exceedingly  minute — probably  a  single  cell  or  a  small 
cellular  group  in  most  cases.  That  epithelial  cells  thus  dissevered  from 
their  normal  connexions  may  still  grow  and  multiply,  we  know  from  the 
familiar  process  of  skin-grafting  ;  and  from  Loeb's  experiments  in  culti- 
vating detached  epithelial  cells  in  blood- serum  etc. 

Probably  all  cancer  cells  are  capable  of  dissemination  ;  but  all  are 
not  capable  of  growing  when  disseminated.  There  are  good  grounds 
for  believing,  that  the  majority  of  these  "  cancer  emboli  "  perish  and 
are  absorbed,  owing  to  the  metabolic  activity  (phagocytosis)  of  the 
cells  of  the  glands  ;  and  that  only  those  with  sufficient  vitality  to  over- 
come this  resistance  originate  dissemination  tumours.  Hence  the 
lymph-glands  form  a  temporary  barrier  to  the  spread  of  the  disease  ; 
and  do  not  themselves  usually  become  affected  until  a  considerable  time 
after  its  primary  outbreak. 

Gussenbauer's  *  histological  researches  confirm  this.  He  found  traces 
of  cancer  cells  disseminated  in  the  glands  of  the  neck,  secondary  to 
primary  disease  of  the  lip,  in  twenty-nine  out  of  thirty-two  consecutive 
cases,  and  doubtful  evidence  of  it  in  the  other  three.  Yet  clinical  experi- 
ence proves,  that  when  the  primary  disease  is  extirpated  without  removal 
of  the  adjacent  glands,  in  a  considerable  proportion  of  cases,  the  latter 
1  Zeitschrift  f.  Heilk.,  1881,  Bd.  ii.,  S.  17. 


414  THE  NATURAL  HISTORY  OF  CANCER 

do  not  originate  recurrences.  Similarly  of  Kuster's1  117  breast-cancer 
extirpations,  in  which  the  excised  axillary  glands  were  microscopically 
examined,  in  only  two  instances  were  they  found  perfectly  free  from 
any  signs  of  cancerous  dissemination  ;  and,  of  six  cases  of  the  same 
disease,  with  no  enlargement  of  the  axillary  glands  clinically  appreciable, 
Gussenbauer  nevertheless  found — on  histological  examination  after 
removal — evidence  of  dissemination  in  these  glands  in  every  case.  But 
we  know  from  clinical  experience  that,  after  extirpation  of  cancerous 
breasts  without  opening  the  axilla,  recurrences  in  the  axillary  glands 
are  proportionately  much  less  frequent  than  this  ;  thus  of  thirteen  mam- 
mary cancers,  with  no  appreciable  enlargement  of  the  axillary  glands, 
for  which  the  breast  alone  was  removed,  Hildebrand  found  that  in 
three,  there  was  no  return  of  the  disease  three  years  and  upwards  after 
the  operation. 

We  have  thus  arrived  at  the  important  conclusion,  that  the  outbreak 
of  the  disease  in  the  lymphatic  glands  is  due  to  cells  detached  from 
the  primary  neoplasm,  arrested  there,  which  subsequently  develop  in 
accordance  with  their  inherent  tendencies.  This  explains  the  great 
resemblance  always  noticeable  between  the  primary  and  secondary 
growths,  the  significance  of  which  it  is  impossible  to  ignore.  Moxon 
has  sagely  insisted  upon  this.  He  says  :  "  The  first  cancer  which  appears 
has  a  likeness  to  the  part  in  which  it  appears,  and  the  secondary  cancers 
arising  from  it  have  the  likeness  of  that  first  cancer ;  and  those  who  doubt 
that  they  came  from  that  first  cancer  must  show  us  why  they  have  that 
likeness.'' 

/fn  this  connexion,  Waring's  experiments  are  of  interest ;  for  they  show 
that  the  cellular  elements,  of  the  secondary,  as  well  as  of  the  primary 
growths,  in  cancer  of  the  pancreas  and  stomach,  produce  the  same 
ferments  etc.  as  the  normal  secretory  cells  of  these  parts. 

In  the  course  of  these  researches  it  has  been  clearly  established,  that 
living  cancer  cells  entering  the  lymphatics  and  lymph-glands,  as  a  rule 
cause  no  coagulation  of  the  lymph  and  no  inflammation  ;  when  therefore 
occurrences  of  this  kind  result,  it  must  be  due  to  septic  material  brought 
by  the  cancer  cells  from  their  original  habitat,  as  not  infrequently  happens. 
Similar  conditions  prevail  when  the  lymphatics  are  invaded  by  continuous 
centrifugal  extension  ;  there  is  no  coagulation  or  inflammation,  unless 
the  invading  cancer  cells  are  contaminated  with  septic  material. 

On  examination  of  affected  glands  removed  at  an  early  stage  of  the 
disease,  it  can  generally  be  made  out  that  the  new  growth  consists  of  but 
a  few  small,  circumscribed  foci,  situated  in  the  peri-follicular  lymph- 
sinuses  of  the  cortex,  or  in  their  immediate  vicinity,  that  is  to  say,  in  the 
course  of  the  normal  afferent  lymph-stream. 

In  a  case  of  melanotic  cancer  of  the  breast  with  secondary  lesions  of 
the  axillary  glands,  the  dark  colour  of  the  cells  enabled  Billroth 2  to 
follow  the  extension  of  the  dissemination  along  the  lymph-sinuses ;  and 
his  observations  have  since  been  confirmed  and  amplified  by  Zehnder.3 

1  Verhand.  der  deutsehe  Oesellschaft.  f.  Chir.,  Bd.  xii.,  S.  288. 

2  Arch.  f.  path.  Anat.,  Bd.  xxi.,  S.  441. 

"Ueber  Krebsentwicklung  in  Lymphdrusen  "  (Arch.  f.  path.  Anat.,  1890,  Bd.  cxix., 
S.  261). 


THE  MORPHOLOGY  OF  MALIGNANT  TUMOURS          415 

The  latter  describes  the  initial  foci  as  increasing  in  size  by  continuous 
proliferation  of  their  constituent  cells,  which  soon  assume  the  alveolar 
arrangement,  just  as  in  the  development  of  the  primary  tumour  in  the 
breast.  These  cells  are  very  rich  in  karyokinetic  figures  ;  and  they  can 
easily  be  distinguished  from  the  cells  (lymphoid)  of  the  parenchyma 
of  the  gland,  which  show  no  signs  of  proliferative  activity,  and  appear 
not  to  participate  in  the  spread  of  the  disease.  Petrick  x  has  arrived 
at  similar  conclusions.  Finally,  by  multiple  staining,  Gibbes  2  has  con- 
clusively demonstrated  the  correctness  of  this  interpretation.  Large 
multi-nucleated  cells,  the  so-called  "  giant  cells  of  cancer,"  are  also  of 
frequent  occurrence.  As  the  cancerous  grafts  increase  in  size,  the 
parenchymatous  cells  of  the  gland  suffer  atrophy  ;  the  bloodvessels  of 
the  stroma  enlarge,  and  their  endothelial  and  muscular  coats  thicken. 
The  endothelial  cells  of  the  lymph  vessels  and  glands  show  no  visible 
alterations,  and  they  evidently  take  no  active  part  in  the  process.  In  its 
subsequent  course  the  disease  progresses  precisely  as  the  primary 
outbreak. 

Although  the  lymphatics  connecting  a  cancerous  tumour  with  the 
affected  glands  are  usually  free  from  disease,  yet  it  occasionally  happens, 
that  they  are  found  distended  with  cancer  cells.  The  so-called  lymph- 
cord,  often  to  be  felt  passing  from  a  mammary  cancer  to  the  axilla, 
is  usually  nothing  but  the  pedicle  of  the  axillary  tail  of  the  mamma 
itself.  The  glands  first  affected  are  usually  those,  that  receive  their 
lymph  directly  from  the  part  of  the  organ  involved  by  the  primary 
neoplasm,  and  the  subsequent  spread  of  the  disease  from  gland  to  gland, 
corresponds  to  the  course  of  the  lymph-stream  ;  but,  it  must  be  borne  in 
mind,  that  each  affected  gland  constitutes  a  new  centre  of  dissemination, 
and  that  the  disseminative  process  may  even  progress  against  retrograde 
lymph  currents  and  valves,  as  is  the  case  when  lymphatics  are  injected 
by  anatomists. 

In  epithelial  cancer  we  seldom  meet  with  any  general  infection  of  the 
lymphatic  system,  such  as  is  often  observed  in  tubercle,  syphilis,  and 
other  infective  diseases.  This  important  fact,  taken  with  the  foregoing 
considerations,  is  an  indication  against  the  resemblance  traced  by  some 
pathologists,  between  these  diseases  and  cancer. 

The  comparative  frequency  of  lymph-gland  dissemination  and  the 
period  at  which  it  is  most  prone  to  supervene,  vary  with  the  type  of 
malignant  disease,  with  locality,  and  even  with  different  varieties  of  the 
same  type  of  cancer  in  the  same  locality.  These  diversities  depend 
chiefly  upon  the  interactions  of  the  following  variable  factors  : — 

(1)  The  size  and  quality  of  the  cancer  cells,  and  their  degree  of 
cohesion  ;  (2)  the  comparative  abundance  or  otherwise  of  the  lymphatics 
in  their  vicinity,  and  the  disposition  of  their  radicles  in  regard  to  the 
cancer  elements. 

It  is  owing  to  the  phagocytic  properties  of  the  invaded  lymph-glands 
that  early  dissemination  is  not  universal ;  and  that  a  temporary  barrier 
is  offered  to  the  spread  of  the  disease. 

1  Deutsche  Zeits.  /.  Chir.,  Ed.  xxxii.,  S.  530. 

2  International  Journal  of  the  Medical  Sciences,  August,  1889,  p.  145. 


416  THE  NATURAL  HISTORY  OF  CANCER 

I  think  there  can  be  no  doubt  that  the  cellular  elements  of  the  epithelial 
tissues  are  more  intimately  connected  with  the  lymph-radicles,  under 
anatomical  as  well  as  under  cancer  conditions,  than  are  the  cellular 
elements  of  the  connective  tissue,  under  similar  circumstances.  Current 
conceptions  as  to  the  relation  of  the  connective  tissue  with  the  lymphatic 
radicles,  are  mainly  based  on  the  histological  researches  of  Reckling- 
hausen  with  nitrate  of  silver  staining  (1862).  According  to  these  obser- 
vations, the  lymphatic  radicles  communicate  freely  with  the  connective- 
tissue  interspaces,  by  means  of  numerous  small  canals  (saft-kanalchen) ; 
and  the  walls  of  the  lymphatics  are  perforated  by  small  pores  (stigmata). 
These  interpretations  of  the  histological  appearances  have  always  been 
objected  to  by  those  anatomists,  who  have  studied  the  lymphatics  by 
injection  experiments,  as  the  material  employed  was  always  found  to  be 
retained  in  the  vessels.  Recent  researches  of  Ranvier  *  and  others,  are 
to  the  same  effect ;  for  they  have  shown  that  the  lymphatics  and  lymph- 
radicles  are  quite  shut  off  from  direct  communication  with  the  sur- 
rounding connective  tissue.  This  is  probably  the  chief  reason  why  local 
and  lymph-gland  dissemination  is  of  more  frequent  occurrence  with 
malignant  epithelial,  than  it  is  with  malignant  connective-tissue  tumours. 
Gross' 2  analysis  of  a  very  large  number  of  cases  of  both  kinds  of 
malignant  tumour  of  the  mamma,  well  illustrates  this  diversity,  as 
follows  : — 

Epithelioma.     Sarcoma. 
Per  Cent.          Per  Cent. 

Invasion  of  the  skin  68'92  9'67 

Invasion  of  chest  wall          ..          ..          ..  21 '58  3'87 

Invasion  of  para-mammary  tissues  . .  8'39  0'64 

Lymph-gland  dissemination  . .          . .  67'35  0'64 

It  is  probable,  however,  that  the  comparative  frequency  of  lymph- 
gland  dissemination  in  mammary  sarcoma,  is  much  greater  than  is 
indicated  by  Gross'  analysis  of  promiscuously  recorded  cases ;  for, 
of  24  consecutive  cases  under  my  observation,3  the  axillary  glands  were 
affected  in  2  ;  of  Poulsen's  4  series  of  33  cases  this  condition  was  found 
in  15  per  cent.  ;  and  of  45  similar  cases  by  Campiche  and  Lazarus-Barlow,5 
the  axillary  glands  were  invaded  in  7. 

Ehrhardt6  reports  dissemination  in  the  adjacent  lymph-glands,  in 
49  of  131  patients  with  malignant  epithelial  tumours  of  the  thyroid  ; 
and  in  18  of  107  patients  with  sarcoma  of  the  same  part. 

Of  10  malignant  epithelial  tumours  of  the  prostate  examined  post- 
mortem, J.  W.  T.  Walker  1  found  that  infiltrated  lymph-glands  were 
present  in  association  therewith,  in  6  cases. 

Of  118  cases  of  primary  epithelial  cancers  of  the  breast  consecutively 
under  my  observation,  there  was  obvious  lymph-gland  dissemination — 
when  the  patients  were  first  seen— in  86,  or  in  73  per  cent. ;  and  of  44 

1  Arch.  d'Anat.  microscopique,  Paris,  1897,  t.  i.,  p.  137. 

2  American  Journal  of  the  Medical  Sciences,  July,  1887,  p.  17. 

3  "  Diseases  of  the  Breast,"  1894,  p.  438. 

4  Arch.  f.  klin.  Chir.,  Bd.  Ixiii.,  S.  592. 

5  Archives  of  the  Middlesex  Hospital,  1905,  vol.  v.,  p.  112. 

6  Bruns'  Beitr.  z.  klin.  Chir.,  1902,  Bd.  xxxv.,  S.  343. 

7  Archives  of  the  MiMleser  Hospital,  1C05,  v>l.  v.,  p.  157. 


THE  MORPHOLOGY  OF  MALIGNANT  TUMOURS          417 

consecutive  necropsies  on  those  M'ho  had  died  of  this  malady,  there  was 
lymph-gland  dissemination  in  40,  or  in  90-9  per  cent. 

From  this  it  follows,  that  dissemination  in  the  adjacent  axillary  glands 
is,  sooner  or  later,  an  almost  invariable  concomitant  of  acinous  (scirrhous) 
cancer  of  the  female  breast ;  the  cases  that  rim  their  entire  course  without 
it  are  of  great  rarity. 

Of  68  cases  of  primary  epithelial  cancer  of  the  mamma  in  males, 
tabulated  by  me,  the  axillary  glands  were  obviously  enlarged  in  43,  or 
in  63  per  cent. 

In  the  corresponding  type  of  cancer  of  the  cervix  uteri,  this  form 
of  dissemination  is  certainly  of  less  frequent  occurrence. 

Thus,  although  a  considerable  number  of  uterine  cancers  run  their 
entire  course,  without  causing  any  obvious  dissemination  in  the  adjacent 
glands,  yet  it  would  be  a  mistake  to  suppose  that  lymph-gland  dis- 
semination is  rare  in  uterine  cancer  ;  for,  as  a  matter  of  fact,  the  adjacent 
glands  are  invaded  in  the  great  majority  of  post-mortem  cases.  Thus, 
of  my  78  necropsies,  lesions  of  this  kind  were  noted  in  56,  or  in  nearly 
72  per  cent.  In  28  per  cent.,  however,  there  was  no  obvious  macro- 
scopical  glandular  affection. 

In  cancer  of  the  corpus  uteri,  local  and  lymph-gland  dissemination 
is  of  slower  and  less  frequent  occurrence,  than  when  the  cervix  is  the 
part  affected  ;  thus,  an  analysis  of  33  necropsies  for  this  form  of  cancer 
by  Andriezen  and  Leitch,  showed  dissemination  in  the  adjacent  lymph- 
glands  in  only  15  cases,  or  in  45  per  cent. 

Malignant  epithelial  tumours  of  the  tongue  and  mouth,  disseminate 
in  the  adjacent  lymph-glands  even  more  frequently  than  cancers  of  the 
breast ;  thus,  of  104  cases  consecutively  under  my  observation,  there  was 
obvious  lymph-gland  dissemination — when  the  patients  were  first  seen — 
in  86,  or  in  nearly  83  per  cent.  ;  and  57  post-mortem  examinations  re- 
vealed lymph-gland  dissemination  in  56,  or  in  98-2  per  cent. 

In  epithelioma  of  the  lower  lip,  this  form  of  dissemination  is  much 
rarer,  and  of  later  advent,  for  of  72  primary  cases  examined  by  me,  when 
first  applying  for  surgical . advice,  only  36,  or  50  per  cent.,  presented 
obvious  enlargement  of  the  adjacent  lymph-glands  ;  and,  of  13  post- 
mortem examinations,  12  revealed  lymph-gland  dissemination,  or  92-3  per 
cent. 

Of  19  cases  of  primary  epidermoidal  cancer  of  the  skin,  the  adjacent 
lymph-glands  were  invaded — when  the  patients  were  first  seen — in  10,  or 
in  52-6  per  cent.  ;  and  of  5  necropsies,  on  those  who  had  died  of  this 
disease,  in  all  the  adjacent  lymph-glands  were  cancerous. 

In  28  cases  of  "  rodent  ulcer,"  I  found  that  the  adjacent  lymph- 
glands  were  invaded  by  the  disease  in  4,  or  in  14-3  per  cent,  (in  all  of  these 
instances  the  disease  was  recurrent)  ;  and,  of  4  necropsies  on  those  who 
had  died  of  this  malady,  none  presented  lymph-gland  dissemination. 

In  cancer  of  the  stomach  the  adjacent  lymph-glands  are  very  often 
invaded.  This  was  the  case  in  89-6  per  cent,  of  N.  Moore's1  29  necropsies  ; 
in  87  per  cent,  of  the  cases  specially  examined  ad  hoc  by  Cuneo  ;2  and  in 

1  Lancet,  1889,  vol.  ii.,  p.  418. 

"  De  1'envahissement  du  systeme  lymphatique  dans  te  cancer  de  1'estomac,"  Paris, 


1900. 


27 


418  THE  NATURAL  HISTORY  OF  CANCER 

70-4  per  cent,  of  H.  ColwelTs1  115  necropsies.  Besides  this,  local  dis- 
semination'in  the  liver,  and  adjacent  parts  was  of  frequent  occurrence. 
^  Renner's2  special  study  of  15  gastric-cancer  cases  gives  similar  results. 
He  very  seldom  found  the  regional  lymph-glands  uninvaded.  The  usual 
mode  of  extension  was  by  the  lymph-channels  :  the  subpyloric  glands 
were  invaded  in  60  per  cent,  of  the  cases,  the  supra-pancreatic  in  49, 
those  of  the  small  curvature  in  45,  the  retro-pyloric  glands  in  42,  those 
of  the  cardia  in  26  per  cent.  ;  and  the  sacral,  lumbar,  and  mediastinal 
glands  in  58  per  cent.,  the  bronchial  glands  in  41,  and  the  mesenteric  in 
22  per  cent. 

In  that  curious  form  of  malignant  disease  known  as  chorio-epithe- 
lioma  or  deciduoma  malignum,  the  precise  status  of  which  has  yet 
to  be  determined,  it  is  noticeable  that — so  far  as  its  disseminative  features 
are  concerned — it  presents  far  more  resemblance  to  sarcoma  than  to 
epithelioma  ;  thus,  notwithstanding  the  very  great  frequency  of  general 
dissemination  in  this  malady,  lymph  -  gland  invasion  is  very  rare, 
Teacher  3  having  found  only  eight  instances  of  this  kind  in  the  numerous 
cases  tabulated,  or  about  4  per  cent. 

These  illustrations  suffice  to  show  the  differences  with  regard  to  lymph- 
gland  dissemination,  between  the  varieties  of  the  epithelial  type  of 
cancer ;  and  similar  diversities  are  also  met  with  among  the  various 
forms  of  sarcoma,  of  wrhich  the  following  examples  will  suffice. 

Of  17  consecutive  cases  of  primary  sarcoma  of  the  upper  jaw  under 
my  observation,  the  adjacent  lymph-glands  were  obviously  enlarged, 
when  the  patients  first  applied  for  surgical  advice,  in  7  cases,  or  in  41-2  per 
cent. ;  and,  of  8  fatal  cases  submitted  to  post-mortem  examination,  in 
4  the  adjacent  lymph-glands  \vere  invaded. 

Sarcomata  of  the  long  bones — the  most  malignant  of  tumours — seldom 
disseminate  in  the  lymph-glands,  although  general  dissemination  occurs 
in  nearly  one-half  of  the  total  cases  ;  thus,  of  Gross'  4  165  cases,  lymph- 
gland  dissemination  was  met  with  only  in  3-7  per  cent.  ;  but,  of  these 
cases,  70  were  myeloid  tumours,  which  very  rarely  spread  to  the  lymph- 
glands. 

Of  36  sarcomata  of  the  long  bones,5  many  of  which  were  under  my 
observation,  adjacent  lymph-glands  were  invaded  in  7,  or  in  19-4  per 
cent.,  only  3  of  these  tumours  being  of  the  myeloid  kind. 

Of  35  sarcomata  of  the  femur  and  tibia6  tabulated  by  Butlin  and 
Colby,7  lymph-gland  dissemination  was  met  with  in  5,  or  in  14-3  per 
cent. 

As  Gross  has  shown,  the  relative  frequency  of  lymph-gland  dissemina- 
tion in  sarcoma  of  the  long  bones,  is  chiefly  dependent  on  the  histological 
structure  of  the  tumour ;  thus,  he  found  that  the  spindle-celled  and 
myeloid  forms  of  the  disease  hardly  ever  caused  lymph-gland  dissemina- 

Archives  of  the  Middlesex  Hospital,  1906,  vol.  vii..  p.  151. 
MiUh.  a.  d.  Grenzgeb.  d.  Med.  u.  Chir.,  Bd.  xxii.,  Heft  2,  S.  131. 
British  Journal  of  Obstetrics  and  Gynaecology,  August,  1903,  p.  145. 
American  Journal   of   the  Medical  Sciences,  July,   1879.      The  initial  seats  were 
femur  in  67,  tibia  47,  humerus  21,  fibula  13,  ulna  7,  radius  6,  radius  and  ulna  in  1  case. 
iemur  17,  tibia  6,  humerus  8,  fibula  3,  and  radius  2 
Femur  22,  tibia  13. 
St.  Bartholomew's  Hospital  Reports,  1895,  vol.  xxvi. 


THE  MORPHOLOGY  OF  MALIGNANT  TUMOURS          419 

tion,   while   with   round-celled   forms   the   adjacent  lymph-glands  were 
invaded  in  from  6-25  to  8-33  per  cent,  of  all  cases. 

Melanotic  malignant  tumours  of  the  skin,  which  have  hitherto 
generally  been  regarded  as  predominantly  sarcomatous,  behave  with 
regard  to  lymph-gland  dissemination  more  like  epithelioma  ;  for,  of  115 
cases  by  Ebermann,  Eiselt,  Coley  and  Pemberton,  I  find  that  48,  or 
41-7  per  cent.,  disseminated  in  the  adjacent  lymph-glands. 

Sarcomata  of  the  uveal  tract,  nearly  all  of  which  are  choroidal — 221  of 
259  according  to  Fuchs — hardly  ever  invade  the  adjacent  lymph-glands, 
although  general  dissemination  is  frequent. 

With  retinal  gliomata,  lymph-gland  dissemination  occasionally 
occurs,  while  general  dissemination  is  rare. 

It  is  stated  of  malignant  tumours  of  the  tonsil  and  testis,  whether  "X- 
epitheliomatous    or    sarcomatous,    that    they    disseminate    with    great 
frequency  in  adjacent  lymph-glands. 

Thus,  of  10  cases  of  primary  malignant  disease  of  the  tonsil,  most  of 
which  were  under  my  observation,  6  were  of  epithelial  and  4  of  connective- 
tissue  origin  ;  of  the  former  group,  the  adjacent  lymph-glands  were 
invaded  in  every  case  ;  and  of  the  latter  group,  in  every  case  save  one. 

Of  12  cases  of  malignant  disease  of  the  tonsil  tabulated  by  Butlin,1 
9  were  of  connective-tissue  and  3  of  epithelial  origin  ;  and  in  all,  save 
one  sarcoma  case,  the  adjacent  lymph-glands  were  invaded. 

With  regard  to  malignant  disease  of  the  testis,  of  20  cases  of  epithe- 
lioma collected  by  Butlin,2  lymph-gland  dissemination  was  found  in 
every  case  fully  examined  ;  and,  of  14  cases  of  sarcoma  similarly  examined, 
only  3  were  exempt  from  this  form  of  dissemination. 

In  the  ovary,  malignant  epithelial  tumours  usually  disseminate  in 
the  adjacent  lymph-glands,  and  this  was  the  condition  in  5  of  9  cases 
under  my  observation  ;  but  sarcomatous  tumours  of  this  part  invade 
the  lymph-glands  less  frequently. 

It  may  be  inferred  from  these  illustrative  details  that  sarcomata, 
as  compared  with  epitheliomata,  rarely  disseminate  in  the  adjacent 
lymph-glands  ;  but  there  seem  to  be  some  exceptions  to  this  rule,  especially 
in  the  tonsil  and  testis,  whence  it  may  be  inferred  that,  in  these  localities, 
the  lymph-radicles  attain  more  intimate  association  with  the  tumour 
elements,  than  is  usual  elsewhere. 

It  is  also  noticeable,  that  the  small  round-celled  and  lymphoid 
varieties  of  sarcoma  are  more  prone  to  invade  the  adjacent  lymph- 
glands,  than  other  forms  of  sarcoma. 

The  number  of  lymph-glands  in  a  given  locality,  commonly  affected 
by  cancerous  dissemination,  often  greatly  exceeds  the  number  of  such 
glands  discriminated  by  anatomists  under  normal  conditions  ;  for  instance, 
about  a  dozen  lymph-glands  are  normally  to  be  found  in  the  axilla  in 
the  course  of  ordinary  dissection,  but,  in  cases  of  mammary  cancer,  the 
number  obviously  noticeable  is  much  greater.  Thus,  in  a  mammary- 
cancer  patient  operated  on  by  Gross,  fifty  diseased  glands  were  removed, 
which  varied  in  size  from  a  small  shot  to  a  large  nut.  I  have  seen  several 
instances,  in  which  the  number  was  nearly  as  great.  This  condition  is 
1  "  Sarcoma  and  Carcinoma,"  1882.  2  Op.  cit. 

27—2 


420  THE  NATURAL  HISTORY  OF  CANCER 

no  doubt  due  to  morbid  enlargement  of  the  numerous,  small,  lymph- 
glandular  structures  normally  present  in  the  axillary  fat,  although 
ordinarily  invisible  to  the  naked  eye. 

The  number  of  glands  usually  affected  is  of  course  much  less  than 
this,  but  hah*  a  dozen  or  more  are  often  obviously  diseased  ;  yet  the 
resulting  tumours  seldom  attain  large  size.  When,  however,  only  a  feu- 
glands  are  involved,  or  but  a  single  one,  tumours  larger  than  usual  often 
ensue.  Cancerous  glands  generally  remain  discrete ;  but  sometimes 
they  blend  together,  forming  a  single  hard,  irregular,  nodular  mass. 

It  is  a  matter  of  considerable  practical  importance  to  determine, 
how  soon  after  detection  of  the  primary  neoplasm,  the  lymph-glands 
become  diseased.  According  to  Fink,1  in  mammary  cancer,  this  happens 
as  early  as  from  the  sixth  to  the  twelfth  month ;  and,  after  the 
thirteenth  month,  the  glands  are  invariably  invaded.  Winiwarter  esti- 
mated the  period  at  from  14  to  18  months.  Gross  gives  the  average 
as  14-7  months.  These  are  but  clinical  data,  which,  of  course,  do  not 
enable  us  to  affirm  that  the  glands  are  free  from  disease  for  the  whole 
period  of  apparent  immunity. 

In  43  of  Kiister's  cases,  with  no  clinically  appreciable  disease  of 
the  glands,  signs  of  cancerous  dissemination  were,  nevertheless,  found 
in  them,  on  histological  examination  after  removal.  On  the  other  hand, 
Poulsen  reports  21  cases  in  which  the  mamma  was  removed  for  cancer — 
the  axilla  not  being  touched — in  which  the  patients  afterwards  remained 
free  from  recurrence  for  three  years,  or  more  ;  although,  in  several  of 
them,  the  disease  had  existed  for  long  periods  prior  to  operation2 
Schmidt  and  others  have  met  with  similar  cases  ;  hence  there  are  evidently 
exceptions  to  the  rule  of  early,  effective,  lymph-gland  dissemination. 

Similar  indications  have  been  met  with  in  cancer  of  the  cervix  uteri. 
As  evidence  of  the  comparative  rarity  of  dissemination  in  the  adjacent 
lymph-glands,  in  the  early  stage  of  this  disease,  reference  may  be  made 
to  the  fact,  that  in  extirpating  cancerous  uteri  surgeons  have  seldom 
met  with  obviously  infiltrated  glands ;  moreover,  after  extirpation, 
glandular  recurrence  is  decidedly  rare. 

According  to  Winter,3  lymph-gland  dissemination  is  present  in 
from  20  to  30  per  cent,  of  all  uterine-cancer  patients  seeking  surgical 
relief  ;  but  Peiser 4  estimates  the  proportion  at  50  per  cent.  ;  while 
Schauta,5  found  lymph-gland  dissemination  in  57-6  per  cent,  of  his  60 
post-mortem  cases,  in  most  of  which  the  disease  had  run  its  natural 
course. 

Recent  experience  of  surgeons  with  the  radical  operation  for  the 
complete  removal  of  the  cancerous  uterus  by  laparotomy,  has  caused 
renewed  attention  to  be  paid  to  this  subject ;  thus,  in  a  series  of  76 

1  Zeits.  f.  Heilkunde,  1888,  Bd.  ix.,  S.  453. 

2  In  one  of  Poulsen's  cases  the  disease  had  existed  for  seven  years  before  operation, 
in  which  only  the  breast  was  removed,  the  axilla  not  being  opened  ;  she  was  well  and  free 
from  recurrence,  when  last  seen,  several  years  afterwards.  Five  other  similar  cases,  in  which 
the  disease  had  lasted  for  several  years  before  removal  of  the  breast,  without  opening  the 
axilla,  were  also  free  from  recurrence  years  afterwards. 

3  Zeitschr.  /.  Geb.  u.  Gyn.,  1893,  Bd.  xxvii.,  S.  101. 

4  Ibid.,  1899,  Bd.  xxxix.,  Heft  2. 

8  Mowtschr.  f.  Qeb.  u.  Gyn.,  1904,  Bd.  xix.,  Heft  4. 


THE  MORPHOLOGY  OF  MALIGNANT  TUMOURS         421 

operated  cases  of  early  cancer  of  the  cervix  uteri,  specially  examined 
ad  hoc,  Wertheim 1  found — on  histological  examination — evidence  of 
cancer  in  22,  or  in  28-9  per  cent.  ;  of  a  number  of  similar  cases  tabu- 
lated by  Wakefield,2  there  was  lymph-gland  dissemination  in  25  per 
cent. 

Yet,  in  spite  of  this  ratio  of  involvement  of  glands  in  the  early  stage 
of  the  disease,  a  considerable  proportion  of  patients  are  found  to  be 
free  from  any  recurrence,  five  years  and  upwards  after  extirpation  of 
the  uterus  by  vaginal  hysterectomy,  in  which  operation  the  lymph- 
glands  are  not  removed  ;  thus,  of  100  operations  of  this  kind,  T.  Wilson  3 
found  that  33  per  cent,  of  his  patients  were  well  and  free  from  recurrence, 
five  years  and  upwards  afterwards,  and  Glockner's  percentage  of  similar 
successful  results  was  35-6  per  cent. 

There  are  then  good  reasons  for  believing,  that  the  majority  of  these 
"  cancer  emboli  "  perish  and  are  absorbed,  owing  to  the  phagocytic 
activity  of  the  lymphocytes  of  the  glands  ;  and  that  only  those  with 
sufficient  vitality  to  overcome  this  resistance,  originate  dissemination 
tumours.  Thus,  the  lymph-glands  form  a  temporary  barrier  to  the 
spread  of  the  disease,  and  do  not  themselves  usually  become  cancerous, 
until  a  considerable  time  after  the  primary  outbreak. 

In  some  very  rare  instances,  glandular  implication  is  so  rapid,  that 
it  appears  to  coincide  with  or  even  to  antedate  the  primary  disease.  In 
others,  it  may  be  delayed  for  several  years — for  ten  years,  or  even  more — 
or  it  may  never  occur  at  all.  Certain  cancers  may  undoubtedly  run 
their  entire  course,  causing  systemic  dissemination  and  death,  without  the 
adjacent  lymph-glands  ever  being  implicated.  Hence,  the  absence  of 
lymph-gland  disease,  is  no  absolute  guarantee  against  general  systemic 
dissemination  ;  which  in  these  cases  evidently  takes  place  through  the 
bloodvessels.  According  to  my  experience,  such  occurrences  are  most 
exceptional  in  unoperated  cases.  I  have  met  with  but  a  single  instance 
of  this  kind,  in  44  consecutive  necropsies  on  patients  who  had  died  from 
mammary  cancer,  there  being  metastases  in  28. 

According  to  Gross,  metastases  occur  without  any  antecedent  lymph- 
gland  dissemination,  in  about  1  in  7  of  all  cases  of  mammary  cancer. 

This  estimate  appears  to  me  too  high,  probably  because  many  opera- 
tion, cases  have  been  included.  Torok  and  Wittelshofer's  figures,  which 
are  much  higher  still,  err  also  from  this  cause. 

In  3  of  the  4  cases  in  my  list,  free  from  lymph-gland  disease,  can- 
cerous axillary  glands  had  just  previously  been  removed  by  operation* 

Should  anyone  oppose  to  this  conclusion  Torok  and  Wittelshofer's 
analysis  of  366  necropsies,  in  which  the  axillary  glands  were  found 
invaded  only  in  175,  or  48  per  cent.  ;  my  answer  is,  that  these  statistics 
are  useless  for  determining  the  point  under  consideration,  because  of  the 
large  number  of  operation  cases  they  include,  in  which  the  affected 
lymph-glands  had  recently  been  removed. 

It  is  commonly  stated  that  the  progress  of  the  disease  is  much  slower, 

1  Cent.  f.  Gyn.,  1901,  No.  2  ;  ibid.,  1902,  No.  9,  etc. 

-   American  Journal  of  Obstetrics,  October,  1903. 

3  British  Journal  of  Obstetrics  and  Gynaecology,  1902,  vol.  i. 


422  THE  NATURAL  HISTORY  OF  CANCER 

and  the  total  duration  of  life  much  longer,  in  cases  where  lymph-gland 
dissemination  is  long  delayed,  than  in  those  where  the  glands  are  attacked 
at  an  early  period  of  the  disease.  I  am  not  aware  of  any  statistical 
evidence  that  can  be  adduced  in  support  of  this  belief  ;  but  my  impression 
is  that  it  is  well  founded. 

It  is,  however,  clearly  shown  by  statistics,  that  obvious  lymph-gland 
affection  is  an  important  factor  in  determining  the  results  attained  by 
operations  for  the  removal  of  the  disease. 

Thus,  according  to  Gross,  of  136  cases  of  extirpation  of  the  breast  for 
cancer,  in  93  obviously  diseased  glands  were  removed  ;  the  total  dura- 
tion of  the  life  of  these  patients  averaged  39-3  months  each,  and  local 
recurrence  ensued  on  the  average  in  1-9  months  ;  whereas,  in  43  cases 
free  from  gland  dissemination,  the  average  duration  of  life  was  52-7 
months,  and  the  average  period  of  recurrence  was  8  months.  The  latter, 
therefore,  lived  13-4  months  longer  than  the  former  ;  and  when  re- 
currence followed,  it  appeared  6-1  months  later. 

Poulsen's  testimony  is  to  the  same  effect,  for  22  per  cent,  of  his 
operated  cases  (in  most  of  which  the  glands  were  not  obviously  affected) 
were  well  for  three  years  or  more,  after  extirpation  ;  whereas,  of  43 
operated  cases  (in  which  the  glands  were  demonstrably  involved),  only 
4  (9-3  per  cent.)  were  well  at  the  end  of  that  period. 

These  data  indicate  that  the  best  time  for  extirpating  the  disease  is, 
before  the  glands  have  become  obviously  involved. 

In  a  certain  proportion  of  these  cancerous  glands,  the  disease  is 
complicated  by  the  supervention  of  inflammation  and  suppuration  ; 
owing,  as  Zahn  x  and  others  have  shown,  to  their  inoculation  with  pyogenic 
microbes,  detached  from  the  primary  neoplasm,  with  the  original  "  cancer 
emboli." 

Lymph-Gland  Dissemination  via  the  Thoracic  Duct. 

A  In  1886  Troisier  2  published  an  essay,  specially  calling  attention  to 
the  frequent  association  of  intra-abdominal  cancer — especially  of  the 
stomach — with  enlargement  of  the  left  supra-clavicular  lymph-glands  ; 
and  insisting  on  the  value  of  this  indication,  "  adenopathie  externe  a 
distance,"  as  a  revealing  symptom  of  intra-abdominal  malignant  disease. 
Cases  of  this  kind  had  previously  been  noted  by  Virchow,  Leube, 
Henoch  and  others  ;  but,  until  Troisier  called  special  attention  to  the 
matter,  neither  clinicians  nor  pathologists  seem  to  have  recognized  its 
importance. 

In  our  country,  this  kind  of  knowledge  has  penetrated  very  slowly, 
notwithstanding  frequent  reminders  from  Troisier  and  others.  The  first 
example  of  it,  recorded  as  such,  was  reported  by  myself  in  1895  ;3  yet 
even  now— such  is  the  lack  of  perspicacity— cases  of  this  kind  are 
generally  regarded  by  British  clinicians  and  pathologists  as  rare  novelties. 

1  Arch.  f.  path.  Anat.,  etc.,  Bd.  cxvii.,  S.  209. 

•  Bull .  et 'Mem.  de  la  Soc.  Med.  des  Htpitaux,  1886,  p.  394;   also  ibid.,  January  13, 
*8  ;   and  Arch.  Gen.  de  Med.,  February  and  March,  1889,  pp.  129  and  297  ;  and  ibid.. 
August,  1893,  p.  423  ;  also  C.  B.  13«  Cong.  Internal,  de  Med.,  Paris,  1900,  t.  iii.,  section 
d'anat.  path.,  p.  42. 

3  Lancet,  1895,  vol.  ii.,  p.  262. 


THE  MORPHOLOGY  OF  MALIGNANT  TUMOURS          423 

In  the  case  referred  to,  the  patient — a  married  woman  aged  fifty- 
six,  the  mother  of  six  children,  having  for  some  months  suffered  from 
progressive  anaemia  and  loss  of  strength,  together  with  failure  of  appetite, 
constipation,  nausea,  and  dyspeptic  symptoms — in  August,  began  also 
to  experience  pain  in  the  epigastric  region,  for  which  she  consulted  a 
medical  man  in  September. 

I  first  saw  her  in  the  following  October,  when  she  was  markedly 
anaemic  and  sallow.  The  ingestion  of  solid  food  caused  epigastric  pain 
and,  after  a  time,  nausea  and  vomiting.  She  complained  of  a  swelling 
in  the  epigastric  region  ;  but,  upon  examination,  no  intra-abdominal 
tumour  could  be  detected.  There  were  no  signs  of  obstruction.  The 
liver  and  spleen  seemed  normal.  There  was  no  history  of  haematemesis 
or  coffee-ground  vomit.  At  this  time,  she  was  very  subject  to  alternate 
flushing  and  pallor  of  the  cheeks  and  extremities,  the  fingers  often 
becoming  quite  dead,  as  in  Raynaud's  disease.  She  was  also  subject  to 
palpitation  of  the  heart,  and  to  occasional  syncopal  attacks.  The  urine 
contained  neither  sugar  nor  albumen.  Under  the  influence  of  rest  in 
the  recumbent  position,  with  none  but  peptonized  fluid  foods,  together 
with,  suitable  medicine,  the  pain  subsided  and  there  was  temporary 
improvement.  It  soon  became  obvious,  however,  that  the  weakness 
was  increasing  ;  and  subsequently  nausea,  vomiting,  and  thirst  became 
prominent  symptoms.  In  the  following  January  I  saw  her  again,  when 
she  was  weaker,  paler,  and  more  sallow  than  on  the  previous  occasion.  I 
was  unable  to  detect  any  intra-abdominal  tumour.  The  case  presented 
many  of  the  features  of  pernicious  anaemia.  She  was  treated  with  "  bone- 
marrow  "  and  Fowler's  solution.  This  treatment  soon  had  to  be  given 
up,  on  account  of  the  pain  and  vomiting  excited.  In  April,  an  intra- 
abdominal  tumour  was  discovered. 

I  saw  her  again  in  May,  when  the  emaciation,  pallor,  and  weakness 
were  very  great.  The  vaso-motor  symptoms  had  quite  disappeared. 
Nausea,  vomiting  and  epigastric  pain,  after  food,  still  continued  ;  but 
there  was  no  haematemesis.  On  abdominal  palpation,  a  circumscribed 
mobile,  intra-abdominal  tumour,  about  the  size  of  a  small  turnip,  could 
be  felt  rather  to  the  right  of  the  median  line,  midway  between  the 
umbilicus  and  xiphoid.  It  was  dull  on  percussion.  There  appeared 
to  be  no  dilatation  of  the  stomach  ;  the  dimensions  of  the  liver  and 
spleen  were  normal ;  there  was  no  umbilical  retraction.  The  left  supra- 
clavicular  lymph-glands,  as  well  as  those  at  the  upper  part  of  the  axilla, 
were  enlarged  and  hard  ;  these,  by  interfering  with  the  venous  circula- 
tion, had  caused  oedema  of  the  face,  head  and  forearm,  this  condition  being 
of  rather  less  than  a  week's  duration.  It  was  evidently  due  to  dis- 
semination of  the  disease  in  the  glands  at  the  root  of  the  neck,  through 
the  medium  of  the  thoracic  duct.  The  recognition  of  this  symptom, 
completely  negatived  any  exploratory  operation.  Death  ensued  about 
five  weeks  later,  and  there  was  no  necropsy.  The  patient  was  partially 
unconscious,  with  muttering  delirium,  for  some  days  before  the  end. 
The  rapid  formation  of  the  tumour,  its  mobility,  the  considerable  size 
attained,  the  absence  of  haematemesis,  gastric  obstruction,  hepatic  and 
splenic  enlargement,  and  finally  the  dissemination  by  the  lymphatics, 


424  THE  NATURAL  HISTORY  OF  CANCER 

all  seemed  to  indicate  malignant  intra-abdominal  tumour— probably  of 
oriental  origin. 

In  this  condition,  some  of  the  superficial  glands  at  a  distance  trom 
the  primary  disease,  become  enlarged,  without  any  of  the  intervening 
structures  necessarily  being  invaded. 

The  glands  usually  thus  affected  are  those  of  the  left  supra-clavicular 
region ;  but  quite  exceptionally  the  right  supra-clavicular,  inguinal, 
axillary,  epitrochlear  or  other  glands  may  be  involved. 

These  may  be  affected  conjointly  with  the  supra-clavicular  glands, 
or  as  isolated  manifestations.  Of  37  supra- clavicular  adenopathies 
tabulated  by  Rousseau,1  in  29  the  glands  of  the  left  side  were  affected  ; 
in  4  those  on  the  right,  and  in  4  those  on  both  sides. 

Although  in  the  majority  of  these  cases,  the  glandular  enlargement 
turns  out  to  be  cancerous  ;  yet  this  is  not  always  the  case,  for  I  have 
witnessed  retrocession,  and  so  has  Girode  :  in  suca  cases  we  probably 
have  to  do  merely  with  septic  infection  from  a  distant  cancerous  growth ; 
and  this  type  of  adenopathy  may  cause  painful  sensations  in  the  neck, 
shoulder  and  arm,  which  are  otherwise  generally  absent. 

But  enlargement  of  the  left  supra- clavicular  glands  may  also  occa- 
sionally result,  from  such  non-cancerous  affections  as  gastric  ulcer, 
tubercle  of  the  lung,  as  well  as  from  other  tuberculous  and  even  syphilitic 
lesions. 

Moreover,  this  adenopathy  must  not  be  confounded  with  the 
•'  pseudo-lipdme  sus-daviculaire "  of  Verneuil,  of  which  I  have  else- 
where given  an  account,2  which  is  simply  an  overgrowth  of  the  fibro- 
fatty  tissue  of  the  supra-clavicular  fossa — both  sides  usually  being 
affected — those  most  liable  being  middle-aged  women  otherwise  in  good 
health. 

At  first,  only  a  single  gland  is  usually  involved,  then  others  of  the 
group  become  affected,  and  these  agglomerate.  Pressure  symptoms 
are  comparatively  rare,  but  I  have  seen  an  instance  in  which  an  affection 
of  this  kind  caused  oedema  of  the  face  and  upper  limb  ;  and  the  lymph 
circulation  through  the  thoracic  duct  may  be  blocked  by  the  glandular 
tumour  compressing  it  in  the  supra-clavicular  vicinity,  as  in  cases  reported 
by  Hillier,  Menetrier  and  Glauckler. 

This  form  of  adenopathy  is  usually  a  late  symptom  ;  but,  in  some 
cases,  it  has  been  known  to  supervene  a  year  or  two  before  death. 

It  seems  probable  that  this  curious  pathological  condition  is  due  to 

regurgitation  of  lymph — charged  with  cancer  cells — from  the  thoracic 

duct,  into  the  adjacent  cervical  glands  ;  which  lymph  is  presumably 

\  conveyed  to  the  thoracic  duct,  by  lymphatics  derived  from  infiltrated 

lumbar  glands. 

It  accords  with  this,  that,  in  these  cases,  cancer  cells  and  cancer 
thrombi  have  often  been  found  free  in  the  thoracic  duct,  without  the 
circulation  through  it  being  arrested  ;  and  this  is  the  usual  condition.  In 
other  cases,  the  duct  is  partially  or  completely  occluded  by  the  growth 
of  cancer  within  it ;  and  thus  it  may  be  reduced  to  the  condition  of  a 

"  De  1'adenopathie  sus-claviculare,"  These  de  Paris,  1895. 
2  Transactions  of  the  Pathological  Society,  London,  1890,  vol.  xli.,  p.  302. 


THE  MORPHOLOGY  OF  MALIGNANT  TUMOURS         425 

solid  cord.  Under  these  circumstances,  chylous  ascites  may  occasionally 
be  met  with.  It  is  astonishing  how  freely  cancer  will  grow  within 
hollow,  circumscribed  structures,  such  as  the  thoracic  duct,  ureter,  veins 
etc.,  when  once  it  has  gained  entry,  and  this  without  necessarily 
implicating  the  encompassing  wall ;  thus,  I  have .  seen  a  case  in 
which  a  process  of  cancerous  growth  from  the  uterus,  having  perforated 
the  lower  end  of  the  ureter,  grew  upwards  in  it  to  the  pelvis  of  the 
kidney,  without  having  invaded  its  walls,  so  that  the  long  cancerous 
process  could  be  removed  entire  from  within  the  ureter,  when  the  latter 
was  laid  open. 

Supra-clavicular  adenopathy  is  fairly  often  met  with  in  the  absence 
of  visceral  dissemination  ;  but,  of  course,  it  generally  implies  antecedent 
invasion  of  the  lumbar  or  other  lymph-glands  discharging  into  the 
thoracic  duct,  although  in  a  few  instances  nothing  of  the  kind  has  been 
noticed  post-mortem. 

I  need  hardly  insist  on  the  importance  of  this  adenopathy,  as  a  contra-  "i6- 
indication  to  operation  ;  and  as  an  element  in  the  diagnosis  of  obscure 
intra-abdommal  disease. 

In  nearly  half  of  the  recorded  cases,  the  seat  of  the  primary  malignant  "/ 
affection  has  been  in  the  stomach  :  instances  of  this  kind  have  been 
reported    by    Troisier,1    Vidal,2    Rousseau,3    Belin,4    Babes,5    Stevens,6 
SpineUi,7  Hillier,8  Menetrier  and  Glauckler,9  Schramm  10  etc. 

Next  to  the  stomach,  most  cases  have  been  met  with  in  association 
with  uterine  cancer  ;  examples  of  this  kind  have  been  noted  by  Troisier, 
Spinelli,  Rousseau,  Faidherbe,  Petit,11  Kirmisson,12  Hillier,13  Unger,14 
Raymond  15  etc. 

Secondary  to  cancer  of  the  pancreas,  Troisier's  symptom  has  been 
seen  by  Nathan  Raw  16  and  Schramm. 

Troisier  and  Poncet 17  have  noted  its  concomitancy  with  cancer  of 
the  testis ;  Hurlemont l8  with  cancer  of  the  prostate  ;  Hillier  with  sar- 
coma of  the  ischio-rectal  fossa  ;  Troisier  with  malignant  disease  of  the 
adrenal  etc. 

Viannay 19  has  directed  attention  to  the  value  of  inguinal  adenopathy, 
as  a  revealing  symptom  of  many  pelvic  and  abdominal  forms  of  malignant 
disease.  In  more  than  a  quarter  of  all  cases  of  uterine  cancer,  I  found 
that  the  inguinal  glands,  of  one  or  both  sides,  were  obviously  enlarged  : 
in  cancer  of  the  cervix  this  is  generally  a  late  sign,  but  when  the  disease 

1  Op.  cit.  2  Butt,  et  Mem.  de  la  Soc.  Med.  des  Hdpitaux,  December,  1893. 

3  Op.  cit.  4  "  Des  adenopathies  externes  a  distance,"  These  de  Paris,  1888. 

5  Ann.  de  I' Hist.  Path,  de  Bucharest,  1894-1895,  t.  vi.,  p.  405. 

6  British  Medical  Journal,  1905,  vol.  i.,  p.  929. 

7  Rivista  di  Clinica  e  Terapia,  1893,  No.  8,  p.  397. 

8  Archives  of  Middlesex  Hospital,  1904,  vol.  iii.,  p.  117. 

9  Butt,  et  Mem.  de  la  Soc.  Med.  des  H6pitaux,  1902. 

10  Berlin,  klin.  Woch.,  October  26,  1896. 

11  Bull,  et  Mem.  de  la  Soc.  Med.  des  Htpitaux,  1888,  t.  v.,  p.  26. 

12  C.  R.  Soc.  Anat.  de  Paris,  1875, 1.,  p.  571. 

13  Op.  cit.  14  Arch.  f.  path.  Anat.,  1896,  Bd.  cxlv.,  S.  58. 

15  Butt.  et.  Mem.  de  la  Soc.  Med.  des  Hopitaux,  1886,  t.  iii.,  p.  441. 

16  British  MedicalJournal,  1905,  vol.  i.,  p.  1380. 

17  Lyon  Med.,  December  31,  1893. 

18  "  De  1'adenite  sus-clav.  cancereuse  dans  le  carcinome  de  la  prostate,"  These  de  Litte, 
1896.  *»  Lyon  Med.,  September  22,  1901. 


426  THE  NATURAL  HISTORY  OF  CANCER 

starts  at  or  near  the  fundus,  these  glands  may  become  affected  at  a  com- 
paratively early  stage  of  the  disease.  Viannay  found  inguinal  adenopathy 
noted,  in  25  of  60  collected  cases  of  cancer  of  the  prostate  ;  and  in 
9  of  62  cases  of  cancer  of  the  bladder.  I  found  the  inguinal  glands 
enlarged  in  12  of  42  cases  of  cancer  of  the  rectum. 

Inguinal  adenopathy  has  also  been  noted  in  association  with  cancer 
of  the  vagina,  anus,  ovary,  stomach,  large  and  small  intestine,  liver, 
pancreas,  and  even  sometimes  with  cancer  of  the  oesophagus  and  other 
intra-thoracic  organs. 

Whippham  *  has  described  an  example  of  cancer  of  the  appendix 
cseci,  with  supra-clavicular  and  inguinal  adenopathy. 


General  Dissemination. 

The  appearance  of  cancerous  growths  in  various  parts  of  the  body, 
remote  from  the  primary  disease  and  its  offsets — the  so-called  metastasis  2 
— is  one  of  the  most  striking  features  of  malignant  tumours,  the  com- 
monest seats  of  these  disseminative  lesions  being  the  liver,  lung,  osseous 
system,  kidney,  brain,  pancreas  etc.  As  mentioned  in  the  opening 
chapter  of  this  work,  there  is  nothing  specific  of  malignancy  in  dissemina- 
tion per  se. 

-f-  Do  benign  tumours  ever  disseminate  in  this  way  ;  and  can  such 
dissemination  originate  from  the  constituent  elements  of  parts  free  from 
any  kind  of  tumour  ? 

If  we  look  only  at  the  conclusions  of  those  who  have  made  special 
study  of  the  remarkable  series  of  events  comprised  under  such  headings 
as  "  deportation  of  chorionic  villi,"  "  deciduoma "  benignum  and 
malignum  etc.,  we  shall  be  constrained  to  answer  both  of  these  queries 
in  the  affirmative. 

Of  similar  import  is  the  occurrence  of  large  cancerous  tumours  in 
lymph-glands  and  in  internal  organs,  secondary  to  primary  lesions  so 
minute,  unprogressive  and  unlike  cancer,  as  hardly  to  be  revealed  even 
by  skilled  examination  ad  hoc,  of  which  many  striking  examples  have 
been  reported,3  and  some  I  have  myself  seen. 

Similar  inference  may  be  drawn  from  the  many  instances  known  to 
me,  of  malignant  disease  developing  in  the  track  of  operation  wounds,  at 
various  periods  after  the  removal  of  non-malignant  tumours,  of  which 

1  Lancet,  February  2,  1901. 

2  The  term  "  metastasis  "  was  originally  applied  to  these  manifestations,  under  the 
belief  that  the  disease  really  shifted  from  one  part  to  another  ;  and,  as  a  matter  of  fact, 
some  local  diminution  of  the  primary  lesion  commonly  coincides  with  the  outbreak   of 
general  dissemination.     The  term  originated  in  general  pathology,  and  was  subsequently 
imported  into  tumour  pathology  ;  in  the  former,  its  use  was   suggested  by  such  morbid 
manifestations  as  are  often  seen  in  mumps,  when  an  outbreak  of  testicular  inflammation 
not  unfrequently  follows  the  subsidence  of  the  original  parotid  malady,  etc. 

3  J.  Hutchinson  (Archives  of  Surgery,  January,  1891,  p.  220  ;  and  April,  p.  349), 
cutaneous  melanotic  staining  with  dissemination  ;  Butlin  (British  Medical  Jmirnal,  1892, 
vol.  n.,  p.  1343),  epidermoidal  cancer  of  the  lymph-glands  of  the  groin  in  a  chimney- 
sweep, with  no  obvious  primary  cancer  of  the  scrotum  or  elsewhere  ;  Paget  ("  Lectures 
on  Surgical  Pathology,"  vol.  ii.,  1853,  p.  447)  has  described  a  similar  case.     I  have  seen 
an  analogous  condition  in  the  lymph-glands  serving  the  lower  lip,  the  latter  part  being 
cancer-free.     For  further  reference  to  this  subject,  vide  Chapter  XXIII. 


THE  MORPHOLOGY  OF  MALIGNANT  TUMOURS          427 

numerous  examples  have  been  recorded  of  late,  after  the  removal  of  non- 
malignant  cystic  tumours  of  the  ovary,  uterine  myomata  etc. 

It  also  seems  to  me  that  certain  exceptional  instances  of  the  late 
recurrence  of  cancer,  point  in  the  same  direction  ;  thus,  in  a  case  reported 
by  Schmidt,1  seven  years  after  extirpation  of  a  primary  cancer  of  the 
breast,  without  local  recurrence,  the  disease  recurred  in  the  liver  ;  and, 
I  am  indebted  to  the  late  Mr.  Hulke,  for  the  knowledge  of  a  similar 
occurrence,  more  than  ten  years  after  extirpation  of  an  eye  for  spindle- 
celled  sarcoma  of  the  choroid,  without  local  recurrence.2 

Here  also  mention  may  be  made  of  the  pseudo-plasms  due  to  yeast 
infection,  described  by  Busse  and  Curtis,3  which  disseminated  in  their 
human  hosts  ;  and  also  caused  disseminative  tumours  in  the  animals  into 
which  they  were  inoculated.  The  similar  tumours  caused  in  various 
animals  by  inoculation  with  certain  pathogenic  yeasts — as  described  by 
Sanfelice  and  his  followers — many  of  which  disseminated,  also  belong 
here.  Moreover,  many  instances  of  dissemination  in  cases  of  mycosis 
fungoides,  have  also  been  reported. 

In  this  connexion  we  must  recoilect  the  contagious  venereal  pseudo- 
plasms  of  dogs  ;  and  the  somewhat  similar  tumours  of  mice  and  rats, 
which  have  lately  attracted  so  much  attention  as  cancer  prototypes,4 
all  of  which  non-cancerous  lesions  are  also  apt  to  disseminate. 

Such  then  are  the  indications,  which  seem  to  point  to  an  affirmative 
answer  to  our  queries. 

On  the  other  hand,  there  is  the  important  fact  that,  in  human 
pathology,  non-malignant  tumours  and  the  elements  of  the  normal 
physiological  tissues,  seem  never  to  originate  metastatic  growths. 

There  are,  however,  some  pathologists  who  challenge  this  apparently 
obvious  proposition,  alleging  that  certain  non-malignant  tumours,  and 
physiological  tissues,  may  indeed  originate  metastases.  Thyroid  adeno- 
mata, and  the  goitrous  thyroid  are  specially  implicated  by  these  allega- 
tions ;  while  claims  of  this  kind  have  also  been  advanced  against  ovarian 
cystic  tumours,  uterine  myoma,  hepatic  adenoma,  cystic  adenoma  of 
the  testis,  chondroma,  osteoma,  lipoma  and  angioma. 

The  controversy  relating  to  this  matter,  concentres  in  the  question 
of  thyroid  metastases  :  these  occur  with  great  frequency  in  malignant 
disease  of  the  thyroid — in  85  per  cent,  of  all  post-mortem  cases,  accord- 
ing to  Ehrhardt,5  the  lungs  and  the  bones  being  their  commonest 
seats. 

According  to  Limacher,  metastases  are  associated  with  malignant 
epithelial  tumours  of  the  thyroid  in  92-1  per  cent,  of  all  cases  ;  and  with 
sarcomata  in  79-5  per  cent. 

1  Bruns'  Beitr.  z.  klin.  Chir.,  Bd.  iv.,  Heft  1. 

2  The  patient  was  an  engineer,   aged  twenty-one,   whose  eye  was  extirpated   by 
Mr.  Hulke  at  the  Royal  London  Ophthalmic  Hospital  on  April  2,  1862,  symptoms  of  the 
disease  having  existed  for  two  years  previously.     In  the  autumn  of  1872,  this  patient  was 
seen  by  Sir  W.  Gull  and  Dr.  Murchison  for  enlargement  of  the  liver,  there  being  then  no 
sign  of  any  recurrence  in  the  orbit.     He  died  some  months  later,  when  the  liver — which 
weighed  20  pounds — was  found  to  contain  huge  masses  of   spindle-celled  sarcomatous 
growth. 

3  Vide  Chapter  X.  *  Vide  Chapter  VTII. 
5  Brims'  Beitr.  z.  klin.  Chir.,  1902,  Bd.  xxxv.,  S.  343. 


428  THE  NATURAL  HISTORY  OF  CANCER 

With  the  epithelial  type  of  malignant  disease,  the  lungs  are  invaded 
in  42  per  cent.,  the  bones  in  29  per  cent.,  and  other  parts  in  order  of 
decreasing  frequency  as  follows : — the  kidney,  pleura,  brain,  liver, 
omentum,  adrenal,  myocardium,  pericardium,  intestine,  ovary,  mamma, 
diaphragm  and  stomach. 

With  the  sarcomata,  the  lungs  are  invaded  in  48  per  cent.,  the  bones 
in  18  per  cent.,  and  the  other  parts  as  follows  : — liver,  kidney,  pleura, 
brain,  myocardium,  intestine,  adrenal,  spleen,  stomach  and  pancreas. 

Of  the  bones  affected,  the  following  analysis  of  75  cases,  indicates 
the  special  proclivities  : — skull  31,  inferior  maxilla  30,  sternum  18, 
vertebra  16,  rib  12,  femur  11,  humerus  10,  pelvis  9,  scapula  4,  zygoma  3, 
clavicle  1  and  palate  1. 

Cohnheim  1  was  the  first  who  maintained  that  metastases  arose  from 
"  simple  goitre  ";  and,  since  the  report  of  this  case  appeared,  about  a 
score  of  others — of  similar  import — have  been  published. 

Recklinghausen 2  declined  to  accept  Cohnheim's  "simple  goitre" 
as  such,  maintaining  that  it  was  a  "  jelly  carcinoma,"  and  Wolfler3  was 
of  the  same  opinion. 

Since  then,  the  various  investigators  have  been  much  divided  in 
opinion,  as  to  the  real  character  of  the  primary,  as  well  as  of  the  secondary, 
lesions,  i  ^ 

Here  it  must  be  noted  that  the  difficulty  in  discriminating  between 
normal  thyroid,  goitrous  thyroid,  thyroid  adenoma  and  thyroid  cancer, 
is  admitted  by  all  experts  to  be  very  great :  thus  Hugnenin  says  :  "  But 
few  features,  upon  which  the  distinction  is  usually  based  in  differentiating 
benign  and  malignant  tumours  of  other  parts,  can  be  relied  on  for  differ- 
entiating between  benign  and  malignant  tumours  of  the  thyroid." 
Berry  4  likewise  writes  :  "  Instances  are  not  unknown  of  simple  adenoma 
being  described  as  carcinoma,  while  obviously  malignant  infiltrating 
tumours  have  been  pronounced  to  be  adenomas.  Even  those  who  have 
had  large  experience  in  the  microscopic  examination  of  thyroid  tumours 
will  admit,  that  it  is  often  difficult  to  say  where  adenoma  ends  and 
carcinoma  begins." 

Another  source  of  fallacy  arises  from  the  well-known  fact  that,  in 
thyroid  cancer,  the  initial  lesion  is  often  so  small  as  to  escape  notice,  even 
after  careful  macroscopic  and  microscopic  examination  of  the  part : 
thus  Hugnenin,  having  had  occasion  to  examine  a  case  of  reputed 
"  colloid  goitre  "  with  dissemination  in  the  dorsal  vertebrae,  found  after 
prolonged  research  a  minute  primary  cancerous  tumour  in  the  goitrous 
gland.  In  reference  to  this  matter  Hugnenin  says  :  "  All  the  hitherto 
published  cases  of  struma  and  thyroid  adenoma,  with  metastasis,  I  regard 
as  being  really  cancerous." 

It  accords  with  this  interpretation,  that  the  localities  invaded  and 
the  character  of  the  lesions,  in  these  secondary  tumours  of  so-called 
non-malignant  thyroids,  are  similar  to  those  met  with  in  undoubted  cases 
of  primary  thyroid  cancer.  For  a  fuller  account  of  cases  of  alleged 

1  Arch.  f.  path.  Anat.,  1876,  Bd.  Ixviii.,  S.  547.  2  Ibid.,  Bd.  Ixx. 

3  Arch.  f.  klin.  Chir.,  1883,  Bd.  xxiv.,  S.  754. 
"  Diseases  of  the  Thyroid  Gland,"  1901,  p.  199. 


THE  MORPHOLOGY  OF  MALIGNANT  TUMOURS          429 

non-malignant  thyroid  metastasis,  reference  may  be  made  to  the  publi- 
cations of  Patel,1  Hansel,2  Coats,3  H.  Morris  4  and  Haward.5 

Similar  objections  hold  against  the  occurrence  of  non-malignant 
metastasis  in  other  parts  of  the  body  ;  and,  in  my  book  on  "  Uterine 
Tumours,"6  I  have  specially  indicated  the  fallaciousness  of  the  facts 
adduced  to  this  end,  with  regard  to  uterine  myoma. 

From  a  general  review  of  the  ensemble  of  the  subject,  I  conclude  that 
the  evidence  hitherto  adduced  for  non-malignant  metastasis  is  incon- 
clusive ;  and  that  the  few  instances  in  which  it  is  alleged  to  have  occurred, 
are  capable  of  being  otherwise  explained. 

The  precise  period  at  which  the  onset  of  general  dissemination  is 
likely  to  supervene  is  variable  ;  but  it  is  usually  of  rather  tardy  develop- 
ment, in  respect  to  the  average  duration  of  life  of  the  particular  variety 
of  malignant  disease  under  my  consideration.  Thus,  with  malignant 
epithelial  tumours  of  the  female  breast — in  which  form  of  cancer  the 
average  duration  of  life,  according  to  my  calculation,  is  from  four  to  five 
years7 — metastasis  may  be  expected  to  supervene  some  two  or  three 
years  after  the  initial  outbreak,  and  about  fifteen  months  after  invasion 
of  the  axillary  lymph-glands.  Winiwarter,  Sprengel  and  Fink  estimate 
its  date  of  onset  at  twenty-five  months,  Henry  at  thirty,  and  Oldekop 
at  thirty-eight  months.  As  a  rule,  the  slower  the  progress  of  the  primary 
disease,  the  later  metastases  appear.  Occasionally  they  form  during 
the  first  few  months  ;  and  at  other  times  not  until  after  the  lapse  of  several 
years — even  ten  years  or  more. 

According  to  Gross,  of  100  metastases  secondary  to  cancer  of  the 
female  breast,  24  form  within  the  first  year,  3  in  from  thirteen  to  eighteen 
months,  18  in  from  nineteen  to  twenty-four  months,  27  in  from  twenty- 
five  to  thirty-six  months,  and  28  after  three  years. 

The  average  duration  of  life  in  this  local  variety  of  cancer,  after  the 
first  appearance  of  metastasis,  is  about  two  years. 

In  the  ensemble  of  their  characters — histological  and  otherwise — 
metastatic  cancers  closely  resemble  the  primary  neoplasm  ;  and  when 
they  differ  it  is  generally  per  defectum.  Thus,  the  hard  and  fibrifying 
primaries,  comparatively  often  originate  softer  and  more  cellular 
secondaries  ;  and,  although  black  cancers  generally  cause  black  meta- 
stases. green  cancers  green  metastases,  and  similarly  with  ossifying,  calcify- 
ing, chondrifying  and  other  varieties,  yet,  in  the  secondaries,  these  special 
features  are  sometimes  deficient  or  they  may  be  altogether  lacking. 

Very  exceptionally,  however,  we  see  the  converse  of  this  ;  for,  as 
Virchow  has  shown,  some  cancers — not  obviously  pigmented — may 
nevertheless  give  rise  to  metastases  in  which  pigmentation  is  a  marked 
feature.8 

1  Rev.  de  Chir.,  1904,  t.  xxxix.,  No.  3,  p.  399. 

2  Beitr.  z.  klin.  Chir.,  1899,  Bd.  xxiv.,  Heft  i. 

3  Transactions  of  the  Pathological  Society,  London,  1887,  vol.  xxxviii.,  p.  399. 
*  Ibid.,  1880,  vol.  xxxi.,  p.  259. 

5  Ibid.,  1882,  vol.  xxxiii.,  p.  291.  6   Vide  p.  88. 

"  Diseases  of  the  Breast,"  1894,  p.  365. 

8  R.  L.  Thompson  has  described  an  instance  of  choroidal  sarcoma,  partly  pigmented 
and  partly  non-pigmented,  which  gave  rise  to  metastases,  some  of  which  were  pigmented, 
some  non-pigmented,  and  others  in  which  these  two  varieties  were  mixed. 


430  THE  NATURAL  HISTORY  OF  CANCER 

Metastatic  tumours  also  differ  somewhat  from  their  primaries  in  their 
relations  to  the  surrounding  tissues— in  that  they  are  generally  more 
circumscribed,  and  less  infiltrating  in  their  mode  of  growth. 

They  also  differ  from  the  latter,  in  that  they  are  usually  multiple 
and  spring  up  in  several  widely  separated  localities.  Occasionally  the 
number  of  metastases  is  very  small ;  and  in  rare  instances  there  may  be 
only  a  single  one,  as  in  a  case  reported  by  Arnott,1  in  which  epithelioma 
of  the  tongue  disseminated  in  the  left  adrenal.  In  soft,  vascular  organs, 
like  the  liver,  these  growths  often  attain  immense  size  ;  but  in  other 
parts  they  are  commonly  of  moderate  dimensions.  Usually  they  pre- 
sent as  small,  hard,  nodular,  flattened  or  discoidal  masses,  which  soon 
become  cupped  or  umbilicated,  owing  to  contraction  of  the  older  parts 
of  the  growth.  Occasionally  they  take  the  form  of  diffuse  infiltrations, 
especially  in  the  pleura,  peritoneum  and  bones. 

In  hollow  structures  such  as  the  cavities  of  the  heart,  the  large  veins, 
the  thoracic  duct,  and  in  the  pleural  and  peritoneal  sacs,  free  masses  of 
metastatic  cancer — generally  embedded  in  more  or  less  coagulum — have 
often  been  found. 

Sometimes  these  growths  are  exceedingly  numerous,  and  widely 
spread  throughout  the  body,  as  in  Velpeau's  2  remarkable  case  of  mam- 
mary cancer,  in  which  hundreds  of  them  were  found  distributed  through- 
out the  general  connective  tissue,  lungs,  liver,  bones,  muscles,  heart, 
stomach,  duodenum,  small  intestines,  pancreas,  kidneys,  gall-bladder, 
vena  cava,  peritoneum,  dura  mater  and  thyroid  gland. 

Similar  cases  have  since  been  recorded  by  Bramwell3  and  Kautor- 
owicz.4 

I  have  seen  it  stated  by  good  authorities,  that  metastases  invariably 
affect  both  of  paired  organs  ;  but  I  have  convinced  myself  by  repeated 
observations,  that  it  is  not  so  :  both  are  usually  affected,  but  often 
only  one. 

It  is  remarkable  that  the  cancers  of  every  locality  have  their  own 
special  modes  of  dissemination  ;  and,  even  the  different  types  and  varieties 
of  the  disease,  in  particular  organs,  manifest  diversities  in  this  respect. 

The  sequence  of  the  development  of  metastases  and  the  combinations 
of  organs  invaded,  are  difficult  to  explain.  The  deep  parts  of  the  body 
are  much  more  frequently  invaded  than  the  superficial ;  but,  the  order 
of  eruption  in  most  individual  internal  organs,  is  usually  the  converse 
of  this. 

In  consequence  of  these  peculiarities,  before  proceeding  further 
with  our  study  of  dissemination,  it  is  desirable  to  review  briefly  the 
incidence  and  relative  frequency  of  metastases,  as  they  are  met  with  in 
the  chief  local  manifestations  of  the  epithelial  and  connective-tissue 
types  of  cancer. 

1  Transactions  of  the  Pathological  Society,  London,  vol.  xix.,  p.  418. 

"  Traite  des  Maladies  du  Sein,"  Paris,  1854. 
3  Edinburgh  Medical  Journal,  July  and  August,  1894. 
*  Cent.  f.  attg.  Path.,  etc.,  1893,  No.  20. 


THE  MORPHOLOGY  OF  MALIGNANT  TUMOURS 


431 


The  Metastases  of  Malignant  Epithelial  Tumours. 

As  these  lesions  have  been  more  fully  studied  in  connexion  with 
cancer  of  the  female  breast  than  elsewhere,  I  propose  to  begin  the  study 
of  metastasis  with  this  type. 

The  female  breast  is  one  of  those  parts  in  which  the  tendency  of  dis- 
semination is  very  great ;  thus,  of  44  consecutive  necropsies,  many  of  which 
were  made  by  myself,  metastases  were  found  in  28,  or  in  63-1  per  cent. 

This  percentage  would  be  considerably  higher,  but  for  the  fact  that 
10  cases  are  included,  which  had  terminated  fatally  shortly  after  extir- 
pation of  the  local  disease,  and  which  were  therefore  presumably  free 
from  metastasis.  Of  the  remaining  34  necropsies,  in  which  death  ensued 
in  the  natural  course  of  the  disease,  there  were  metastases  in  25,  or  in 
73-5  per  cent. 

Of  these  44  consecutive  necropsies,  the  seats  of  metastases  were  as 
follows  : — 


Liver 
Lungs  (B.  5,  L.  2,  R.  1) 
Pleura  (B.  5,  L.  1) 
Femur  (B.  2,  R.  1,  L.  1) 
Retro-peritoneal  glands 
Bronchial  glands    .  . 
Humerus  (R.  1,  L.  1) 
Kidneys 
Supra-renals  (B.  1,  L.  1) 
Pancreas 
Vertebrae  (lower  dorsal  an 
upper  lumbar) 

ii 
d 

i  20  ca 
8 
6 
4 
3 
2 
2 
2 
2 
2 

,     1  ca& 

ies.       Mesenteric 
glands 
Gastro  -  he 
glands 
Peritoneum 
!   Uterus 
j   Ovary  (L.) 
Tibia  (R.) 
I   Ribs  (B.) 
Spleen 
Duodenum 
e.      '   Mamma  (of 

and  oment. 
patic  oment 

a 

.   i 
a 

n 

1  OM 

opposite  side) 

The  liver  is  the  organ  most  frequently  affected  with  metastases  in 
mammary  cancer.  My  analysis  shows  this  in  a  striking  manner  ;  but,  it 
would  have  been  otherwise,  had  I  not  carefully  separated  the  true  pul- 
monary metastases  from  those  cases  (twelve  altogether),  in  which  the 
lungs  were  invaded  by  direct  extension  of  the  primary  disease  or  by  its 
local  dissemination.  The  discrepancy  between  my  analysis,  and  those 
statistics  which  place  the  lungs  and  pleurae  at  the  head  of  the  list,  is 
evidently  due  to  this  cause. 

Of  470  similar  necropsies  analysed  by  Campiche  and  Lazarus-Barlow,1 
metastases  were  found  in  84-4  per  cent.  ;  while  of  Torok  and  Wittel- 
shofer's2  366  necropsies,  they  were  met  with  in  215,  or  in  58-7  per  cent. 

By  massing  the  totals  of  these  authors  with  Gross'  cases,  we  get  a 
total  of  893  necropsies,  with  metastases  having  the  following  percentage 
distribution  : — liver  46-8,  pleura3  42-4,  lungs3  42,3,  bones4  26-5,  lymph- 
glands5  (exclusive  of  axillary  and  cervical)  19-0,  mamma  (of  opposite 
side6)  12-9,  kidney  7-2,  pericardium  7,  brain  and  meninges  6-6,  ovary  6-5, 
peritoneum  6-2,  stomach  and  intestines  4-9,  supra- renal  4-6,  spleen  3-7, 

1  Archives  of  the  Middlesex  Hospital,  1905,  vol.  v.,  p.  83. 

2  Arch.  f.  klin.  Chir.,  Bd.  xxv.,  S.  873. 

3  I  suspect  many  cases  of  direct  lymphatic  extension  are    comprised  under  these 
headings. 

4  The  percentage  site-incidence  of  these  metastases  were  as  follows :    Cranium   24, 
vertebrae  19'2,  ribs  19'1,  femur  14'5,  humerus  9'3,  innominate  6'5,  clavicle  4'2,  scapula  T2, 
leg-bones  0'9,  forearm  bones  0'45,  and  sternum  0'45. 

5  Inguinal  8'6,  retro-peritoneal  8'3,  bronchial  1*7,  mediastinal  0'4. 

6  No  doubt  instances  of  direct  lymphatic  extension  are  comprised  under  this  heading. 


432  THE  NATURAL  HISTORY  OF  CANCER 

uterus  3-1,  pancreas  2-5,  thyroid  2-5,  heart  1-6,  muscles  0-9,  bladder  0-7, 
omfntum  0-6,  Fallopian  tube  0-5,  venous  system  0-4,  spinal  medulla  0-4, 
facial  nerve  0-4,  vagina  0-2,  oesophagus  0-1  and  ureter  0-1. 

Metastases,  secondary  to  cancer  of  the  breast,  have  also  been  met 
with  in  he  uveal  tract — especially  in  the  choroid  j1  and  mammary 
cancer  has  even  been  known  to  disseminate  in  a  uterine  myoma  (Bender 
and  Lardennois  2). 

In  mammary  cancer,  as  I  have  previously  mentioned,  the  ribs, 
sternum,  and  occasionally  the  clavicle,  and  even  the  upper  end  of  the 
humerus  may  become  cancerous,  through  direct  extension  of  the  primary 
disease  or  through  its  local  dissemination  :  such  cases  have  been  excluded 
from  this  list,  whenever  there  was  sufficient  information  to  warrant  it. 

S.  Coupland3  has  described  a  case  in  which  the  metastases  were 
limited  to  both  ovaries  ;  Colle  and  Paquet 4  to  the  liver  ;  Cruveilhier,5 
Walther,6  Letienne,7  Arnott,8  and  Hillier,9  to  the  osseous  system. 

Of  40  intra-cranial  metastases  in  Torok  and  Wittelshofer's  analysis, 
the  parts  affected  were  :  dura  mater  in  25,  cerebrum  in  22,  cerebellum 
in  13,  pia  mater  in  3,10  and  pineal  body  in  2  cases. 

It  is  noteworthy  that  the  incidence  of  metastases  in  cancer  of  the 
breast,  in  males,  is  similar  to  that  which  we  have  seen  holds  in  the  case 
of  females  :  thus,  of  10  necropsies  analysed  by  me,  there  were  metastases 
in  7,  or  in  70  per  cent.  These  were  located  as  follows  : — in  the  liver. 
3  cases,  lungs  and  pleura  (both  2,  right  1)  3  cases,  bones  3  cases,  kidney 
(both)  in  1  case,  bladder  1,  peritoneum  1,  stomach  (cardiac  end)  1,  and 
pancreas  in  1  case.  The  following  were  the  bones  involved  : — both 
clavicles  and  tibia  in  1  case,  vertebrae  and  other  bones  in  1  case,  and  the 
sphenoid  with  the  base  of  the  skull  in  1  case. 

The  following  analyses  give  a  good  idea  of  the  relative  frequency 
and  site-incidence  of  metastases,  secondary  to  cancer  of  the  cervix  uteri. 

Of  79  consecutive  necropsies,  I  found  that  dissemination  had  taken 
place  in  16,  or  in  20-2  per  cent.  ;  thus  the  cervix  uteri  is  one  of  those 
parts,  in  which  the  liability  of  cancer  to  disseminate  in  distant  localities 
is  not  very  great.  The  probable  explanation  of  this  difference  is,  that 
patients  with  cancer  of  the  cervix  are  commonly  cut  off  by  fatal  inter- 
current  complications,  before  the  cancerous  disease  has  had  time  to 
mature  ;  for  this  form  of  dissemination  seldom  sets  in,  until  .a  com- 
paratively late  stage  of  the  disease.  It  accords  with  this,  that  meta- 
stases are  of  more  frequent  occurrence  with  cancer  of  the  corpus  uteri, 

1  Of  31  metastatic  choroidal  cancers  tabulated  by  H.  Parsons,  in  24  the  primary 
cancer  was  mammary. 

2  Bull,  et  Mem.  Soc.  Anat.,  Paris,  October,  1904. 

3  Transactions  of  the  Pathological  Society,  London,  vol.  xxvii.,  p.  26  ;  for  a  some- 
what similar  case  by  Nadig,  vide  Bev.  de  Gyn.  etde  Chir.  Abd.,  January  and  February,  1903. 

4  L'Echo  Mid.  du  Nord,  1906,  Xo.  23,  p.  160  :  it  was  thought  to  be  a  case  of  primary 
multiplicity. 

'   Vide  my  book  on  "  Diseases  of  the  Breast,"  p.  200. 

6  Ibid. 

7  Butt.  Soc.  Anat.,  Paris,  1890,  p.  425. 

*  Transactions  of  the  Pathological  Society,  London,  vol.  xix.,  p.  356. 

^  Archives  of  the  Middlesex  Hospital,  vol.  iii.,  p.  122. 

For  instances  of  dissemination  in  the  cerebral  and  spinal  rneninges,  peripheral 
nerves  etc.,  wdePeabody  (Transactions  of  the  Association  of  American  Physicians,  1907, 
vol.  xxii.,  p.  17). 


THE  MORPHOLOGY  OF  MALIGNANT  TUMOURS 


433 


when  the  average  duration  of  the  patient's  life  is  considerably  longer, 
than  in  the  cervical  form  of  the  disease. 

The  seats  of  these  metastases  were  as  follows  : 


Lungs  (both  6,  right  1) 

Liver  

Peritoneum  and  omentum 

Pleura  (both  1,  right  1) 

Skin  of  chest  and  abdomen 

Tibia  (right)  and  innominate  bone  (right) 

Heart  

Kidney  (left)          

Ureter   (left)  

Bronchial  glands 


in    7  cases. 
7 
4 
2 

1  case. 
1 
1 
1 
1 


Dissemination  in  the  bones  is  rare  in  uterine  cancer  ;  but,  in  addition 
to  the  case  included  in  the  foregoing  analysis,  I  know  of  instances  in  which 
it  has  occurred  in  the  femur,1  humerus,2  and  ribs  3  respectively. 

Of  187  similar  necropsies,  analysed  by  Andriezen  and  Leitch,4  meta- 
stases were  found  in  20-4  per  cent. 

Their  site-incidence  and  percentage  distribution  were  as  follows  : — 
liver  13-5,  lung  6,  peritoneum  5,  kidney  2-6,  supra-renal  1-9,  pleura  1-4, 
heart  1,  bones5  0-9,  stomach  and  intestines  0-9,  pancreas  0-9,  diaphragm 
0-7,  gall-bladder  0-6,  abdominal  wall  0-4,  thoracic  wall  0-3,  subcutaneous 
0-3,  pericardium,  thyroid,  oesophagus  and  mamma  of  each  0-1. 

Other  parts  sometimes  implicated  by  the  dissemination  of  this  form 
of  cancer  are  the  brain,  dura  mater  and  skin. 

Of  33  necropsies,  by  the  same  authors,  for  cancer  of  the  corpus  uteri, 
metastases  were  met  with  in  15,  or  in  48-5  per  cent.  :  the  seats  of  these 
lesions  weie — the  liver  (15  per  cent.),  lungs  (15  per  cent.),  intestine  (12  per 
cent.),  spleen,  pericardium,  pleura,  diaphragm  and  ribs  (each  in  3  pet 
cent.).  The  peritoneum  was  involved  in  27  per  cent,  of  these  cases. 

Schiller  6  has  lately  reported  an  instance  of  metastatic  cancer  of  both 
knee-joints,  which  supervened  eight  weeks  after  abdominal  hysterectomy 
for  this  kind  of  cancer. 

Of  10  necropsies  for  cancer  of  the  prostate,  analysed  by  Walker,7 
metastases  were  noted  in  6  ;  the  parts  affected  being  the  liver  in  3,  and 
the  lungs  in  3  cases — while  the  pancreas,  adrenal,  kidneys,  testis,  peri- 
toneum and  colon,  were  also  involved,  each  in  1  case. 

It  is  noteworthy  that,  in  this  series,  not  a  single  example  of  dis- 
semination in  the  osseous  system  was  found  ;  yet,  according  to  Kaufmann 

1  St.  Bartholomew's  Hospital  Report,  1888,  p.  389  :  "  Cancer  of  cervix  uteri,  with  dis- 
semination in  the  left  femur." 

2  University  College  Hospital  Report.  1888,  pp.  92  and  142  :   "  Cancer  of  the  cervix 
uteri,  with  dissemination  in  the  upper  part  of  the  right  humerus,  which  was  mistaken  for 
primary  sarcoma,  for  which  the  upper  limb  was  amputated  at  the  shoulder- joint  "  ;  vide 
also    Transactions    of    the    Pathological    Society,  1886,  vol.  xxxvii.,  p.  379,    for    what 
appears  to  be  a  similar  case. 

3  "Catalogue  of  the  Middlesex  Hospital  Museum,"  p.  69,  No.  600:  "Cancer  of  the 
cervix  uteri  with  dissemination  in  the  ribs." 

;  "  Archives  of  Middlesex  Hospital,"  1906,  vol.  vii.,  p.  165. 

6  The  bones  implicated  were — vertebra*.  2  cases  ;  innominate,  2  cases  ;  skull,  ribs, 
and  tibia  of  each  1  case.  Billroth  and  Leucke  found  metastases  in  the  bones  in  5 
of  their  166  uterine-cancer  necropsies,  or  in  3  p«r  cent. 

6  Monats.  f.  Geb.  u.  Oyn.,  June.  1907,  S.  953. 

7  "Archives  of  Middlesex  Hospital,"  1905   vol.  v.,  p.  157. 

28 


434  THE  NATURAL  HISTORY  OF  CANCER 

and  others,  prostatic  cancer  disseminates  in  the  bones  in  from  13  to 
70  per  cent,  of  all  cases.  But,  spontaneous  fractures  and  other  notice- 
able lesions,  seldom  result ;  so  that  these  metastases  may  easily  be  over- 
looked, unless  the  skeleton  is  specially  examined  ad  hoc,  and  this  explains 
the  divergences  in  the  estimates  as  to  its  frequency.  Thus  Kaufmann 
found  osseous  metastases  in  34  per  cent,  of  the  cases  reported  in  the 
post-mortem  records  ;  but  of  22  cases,  in  which  the  bones  were  specially 
examined,  intra-osseous  metastases  were  found  in  all  but  four. 

The  seats  of  these  osseous  metastases,  in  order  of  relative  frequency 
are  :_the  vertebra,  os  innominatum,  femur,  ribs,  sternum,  skull, 
humerus,  tibia,  scapula,  clavicle,  fibula,  and  bones  of  the  forearm. 

In  further  illustration  of  this  subject,  I  propose  to  examine  the  site- 
incidence  and  relative  frequency  of  metastases  ;  in  the  chief  local  varieties 
of  epithelial  cancer,  thrcmghout  the  alimentary  system. 

In  the  lower  lip  epithelial  cancer  rarely  gives  rise  to  metastasis  ;  for, 
of  13  consecutive  necropsies  many  of  which  were  made  by  myself,  this 
form  of  dissemination  was  met  with  in  only  2  cases,  or  in  15-4  per  cent. 
The  parts  thus  invaded  were,  the  lungs  (right  1,  left  1)  in  2  cases,  and 
the  kidney  (right)  in  1  case. 

Of  57  consecutive  necropsies  for  epithelioma  of  the  tongue  and  mouth 
analysed  by  me,  metastases  were  found  in  7,  or  in  only  12-3  per  cent. 
The  parts  thus  affected  were  the  liver  and  both  lungs  in  2  cases,  both  lungs 
in  2  cases,  the  liver,  left  kidney  and  mesenteric  glands,  each  in  1  case. 

In  the  tonsil  this  type  of  cancer  seems  to  cause  metastases  with  great 
frequency  ;  for,  of  3  necropsies  in  Butlin's l  list,  all  disseminated — 1  in 
the  liver,  1  in  the  lungs  and  1  in  the  thyroid. 

In  the  oesophagus  epithelial  cancer  often  disseminates  ;  thus,  of  14 
consecutive  necropsies  some  of  which  were  made  by  myself,  lesions  of 
this  kind  were  found  in  5,  or  in  35-7  per  cent.,  the  parts  affected  being 
the  liver  in  2  cases,  peritoneum  2  cases,  kidney  (right),  lung  (right),  and 
bladder,  each  in  1  case.  In  2  of  these  cases  the  disease  spread  by  con- 
tinuity from  the  oesophagus  to  the  stomach,2  in  5  cases  to  the  trachea, 
in  3  to  the  bronchus,  in  2  to  the  lung  and  pleura,  and  in  2  to  the  pharynx. 

Of  15  similar  necropsies,  N.  Moore  3  found  metastases  in  the  liver  in 
7,  lungs  in  5,  kidney  in  4,  and  the  pancreas,  spleen  and  adrenal  each  in 
1  case. 

Other  localities  in  which  metastases  have  been  met  with  are,  the  brain 
and  its  membranes,  skin,  and  the  osseous  system  (vertebrae,  femur  and 
sternum). 

The  stomach,  peritoneum,  adjacent  vertebrae,  thyroid,  larynx,  heart 
and  pericardium,  are  fairly  often  invaded  by  direct  extension. 

In  cancer  of  the  stomach,  says  Brinton,4  "  the  liver  is  involved  in  a 

"  Sarcoma  and  Carcinoma,"  1882. 

2  Secondary  cancer  of  the  stomach  is  a  very  rare  affection,  except  when  some  adjacent 
part  of  the  digestive  tract  is  the  seat  of  primary  cancer.     Most  cases  of  this  kind  are 
secondary  to  primary  cancer  of  the  oesophagus.     Thus  of  25  cases  of  secondary  gastric 
cancer  tabulated  by  Castro,  in  18  the  source  of  the  primary  disease  was  in  the  oesophagus. 
Of  the  7  cases  in  which  the  primary  disease  was  situated  outside  the  digestive  tract,  the 
localities  affected  were,  the  female  breast  in  3  cases,  the  eye,  tongue,  testis,  and  leg — 
each  in  1  case. 

3  Lancet,  1889,  vol.  ii.,  p.  417.  *  "  Diseases  of  the  Stomach,"  p.  245. 


THE  MORPHOLOGY  OF  MALIGNANT  TUMOURS          435 

ratio  twice  as  great  as  that  of  such  deposit  in  the  adjacent  lymph-glands, 
and  thrice  as  great  as  that  of  secondary  cancer  of  the  lungs."  In  the 
light  of  recent  researches,  Brinton  certainly  under-estimated  the  fre- 
quency of  lymph-gland  dissemination  in  gastric  cancer  ;  and  the  same  may 
be  said  of  Gussenbauer's  analysis,1  in  which  dissemination  in  the  adjacent 
lymph-glands  was  noted  in  273  of  903  necropsies,  or  in  30  per  cent.2 

In  the  latter  analysis,  dissemination  was  found  in  572  of  the  total 
necropsies,  or  in  63-3  per  cent. — the  liver  being  the  part  involved  in 
259  (28-6  per  cent.),  the  pancreas  in  100  (11  per  cent.),  and  the  peritoneum, 
omentum,  and  intestines  in  173  (19  per  cent.). 

Brinton  estimated  the  frequency  of  dissemination  in  gastric  cancer r 
at  48  per  cent,  of  the  total  necropsies,  and  Lebert  at  40-9  per  cent. 
According  to  Lebert,  the  peritoneum  was  invaded  in  37-5  per  pent.,  the 
liver  in  25  per  cent.,  the  lungs  in  8-3  per  cent.,  and  the  ovaries  in  4-5  per 
cent. 

In  gastric  cancer,  the  liver  and  adjacent  structures  are  no  doubt  very 
frequently  invaded  by  direct  extension  of  the  disease  by  the  lymphatics 
etc.  ;  and  Gussenbauer  notes  that  the  stomach  was  matted  to  neighbour- 
ing structures,  in  394  of  his  903  necropsies. 

In  N.  Moore's  3  careful  study  of  29  gastric-cancer  necropsies,  in  only 
3  cases  was  the  disease  limited  to  the  stomach.  He  notes  its  frequent 
spread  by  continuity  (in  7  cases),  along  the  lymphatics  in  the  vicinity 
of  the  upper  and  lower  borders  of  the  stomach,  to  adjacent  structures, 
e.g.,  to  the  liver,  in  4  cases  ;  to  the  diaphragm,  omentum,  mesentery, 
pancreas  and  transverse  colon — each  in  2  cases  ;  and  to  the  oesophagus, 
ascending  colon,  spleen,  vertebrae,  and  inferior  vena  cava — each  in  1  case. 

Dissemination  in  the  lymph-glands  of  the  hilum  of  the  liver,  lumbar, 
mesenteric  and  mediastinal  regions,  was  noted  in  about  60  per  cent,  of 
the  total  necropsies. 

Besides  these  lesions,  metastases  were  found  in  the  liver  in  2  cases  ; 
and  in  the  heart,  spleen  and  adrenal — each  in  1  case. 

The  latest  research  into  this  subject,  by  Colwell,4  shows  that  of 
115  necropsies  for  cancer  of  the  pyloric  region  of  the  stomach,  metastases 
were  noted  in  81,  or  in  70-4  per  cent.,  the  site  incidence  of  these  lesions 
being  as  follows  : — liver  in  47  cases,  peritoneum  in  29,  pancreas  6,  pleura  5, 
lung  5,  ovary  3,  adrenal  3,  heart  2  ;  pericardium,  intestine,  spleen,  thoracic 
duct,  skin,  ribs  and  vertebrae — each  in  1  case. 

The  liver  was  also  invaded  by  the  direct  extension  of  the  primary 
disease,  in  23  cases,  and  the  pancreas  in  16  cases. 

The  following  lymph-gland  dissemination  was  noted  : — portal  glands 
in  50  cases,  cceliac  in  30,  mesenteric  in  25,  aortic  in  20,  mediastinal  in 
3,  and  axillary  in  1  case. 

Gastric  cancer  has  been  known  to  disseminate  in  the  choroid,5 
the  uterus,6  the  brain,  and  the  skin.  Risel7  has  lately  described  twa 

Arch.  f.  klin.  Chir.,  1876,  Bd.  xix.,  S.  372. 

For  further  details,  vide  p.  417  of  this  chapter.  3  Lancet,  1889,  vol.  ii.,  p.  418.. 

"  Archives  of  Middlesex  Hospital,"  1906,  vol.  vii.,  p.  151. 

H.  Parsons,  "  Pathology  of  the  Eye,"  1905,  vol.  ii. 

C.  £.  Soc.  d'Obstet.  de  Gyn.,  etc.,  Paris,  May,  1905  (Couvelaire). 

Ziegler's  Beitr.  z.  path.  Anat.,  etc.,  1907,  £d.  xlii.,  Heft  2. 

28—2 


436  THE  NATURAL  HISTORY  OF  CANCER 

remarkable  cases  of  gastric  cancer,  in  which  the  disseminative  lesions 
resembled  "  chorio-epithelioma." 

Dissemination  in  the  skeletal  system  is  rare,  since  only  three  instances 
of  it1  were  noted  in  174  consecutive  necropsies  analysed  by  Col  well,  or 
in  1-7  per  cent.  ;  and  not  a  single  example  of  it  is  mentioned  by  the  other 
authors  above  cited.  Cruveilhier,2  however,  long  ago  described  an 
instance,  in  which  the  disease  disseminated  in  the  right  humerus  (with 
spontaneous  fracture)  and  sternum,  there  being  no  other  metastases. 
Perry  and  Shaw3  have  also  found  cancer  of  the  pylorus,  with  spon- 
taneous fracture  of  the  femur  owing  to  cancerous  metastases — the 
liver  and  lungs  also  being  similarly  affected.  Recently  other  instances 
of  this  kind  have  been  published  by  Kurpjuweit,4  Goetsch,5  Zade,c 
Pinatelle  and  Cavaillon.7  In  Goetsch's  case,  the  osseous  system 
was  extensively  invaded — the  cranium,  vertebrae,  ribs,  sternum,  clavicle 
and  pelvic  bones  being  affected,  as  well  as  the  dura  mater  :  in  the  other 
cases,  the  bones  invaded  were  the  third  lumbar  vertebra,  base  of  skull 
and  left  parietal  bone — each  in  1  case. 

Colwell's  analysis  shows  that  ovarian  dissemination  is  rare  in  gastric 
cancer  ;  since  but  five  examples  of  it  were  noted  in  174  consecutive 
necropsies,  or  rather  less  than  3  per  cent.  ;  and  the  other  above-cited 
analyses  are  of  similar  import.8 

Of  late,  however,  a  considerable  number  of  cases  have  been  reported 
in  the  medical  periodicals,  of  bilateral,  large,  solid  ovarian  tumours — 
the  so-called  "  Krukenberg's  tumours " — concomitant  with  gastric 
cancer.  It  is  to  Schlagenhaufer 9  and  Wagner10  that  we  are  specially 
indebted  for  showing,  that  these  tumours  are  sometimes  due  to  cancerous 
dissemination  from  a  primary  focus,  the  usual  seat  of  which  is  in  the 
stomach,  the  intestines  or  elsewhere.  They  had  previously  been  regarded 
as  independent  new  formations  of  endotheliomatous,  fibro-sarcomatous 
or  fibroid  nature.  Of  79  cases  of  this  kind  tabulated  by  Schlagenhaufer, 
in  61  the  primary  focus  was  in  the  stomach,  in  10  in  the  intestine,  and,  in 
the  other  8  cases,  in  various  intra-abdominal  situations. 

It  yet  remains  to  be  proved  whether  most  cases  of  "  Krukenberg's 
tumours,"  concomitant  with  a  malignant  focus  elsewhere,  really  are  of 
metftstatic  nature  ;  or,  whether  most  of  them  may  not  be  of  independent 
origin — bearing  the  same  setiological  relation  to  the  concomitant  can- 
cerous focus,  that  bilateral  ovarian  cystic  disease  often  seems  to  have  to 
"  chorioma  malignum." 

Of  17  necropsies  for  epithelial  cancer  of  the  colon — 9  by  N.  Moore 

and  8  of  my  own  series — metastases  were  found  in  only  4  cases,  or  in 

23-5  per  cent.  :    the  parts  affected  being  the  liver  alone  in  3  cases,  the 

liver  and  lungs  (both)  in  1  case.     In  12  of  these  necropsies  the  disease 

1  Vertebrae,  2  cases  ;  ribs,  1  case.  2  Anat.  Path.,  liv.  xx.,  p.  5. 

3  Guy's  Hospital  Report.  1891,  vol.  xlviii.,  p.  155  (Case  21). 

4  Deuteche  Arch.  f.  klin.  Med.,  1903,  Bd.  Ixxvii.,  S.  552. 

6  Ziegler's  Beitr.  z.  path.  Anat.,  etc.,  1906,  Bd.  Ixxxix.,  S.  218. 

«  Ibid.,  1904.  7  prOV   MM.,  April  14,  1906. 

B  When  cancerous  disease  of  the  stomach  penetrates  the  gastric  wall,  it  may  dissemi- 
nate throughout  the  peritoneal  sac  by  auto-implantation,  invading  the  ovaries,  uterus 
etc.,  as  m  cases  reported  by  Schenk,  to  which  I  have  previously  referred. 

9  Monatschr.  f.  Oeb.  u.  Oyn.  (supplement),  April,  1902,  Bd.  xv. 

10  Wien.  klin.  Woch,,  1902,  Bd.  xv.,  No.  20,  S  519. 


THE  MORPHOLOGY  OF  MALIGNANT  TUMOURS         437 

had  spread  by  direct  continuity  to  adjacent  structures,  as  follows : — 
ileum  in  3  cases,  duodenum  3  cases,  one  ovary  in  2  cases,  stomach  2  cases, 
other  parts  of  colon  2  cases,  abdominal  wall  2  cases  ;  and  to  the  uterus, 
bladder  and  liver — each  in  1  case.  Dissemination  in  adjacent  lymph- 
glands,  was  noted  in  5  of  the  17  necropsies. 

In  cancer  of  the  rectum  metastasis  is  of  much  more  frequent  occur- 
rence, since  of  my  27  consecutive  necropsies,  this  form  of  dissemination 
was  met  with  in  14,  or  in  51-5  per  cent.  ;  the  parts  affected  were,  the 
liver  in  12  cases,  lungs  (both  4,  left  1,  right  1)  in  6  cases,  kidney  (both)  in 
3  cases,  spleen  in  2  cases,  pleura  (both),  ovary  (both),  mamma  (left),  adrenal 
(right),  dorsal  vertebrae  (seventh  and  eighth)  and  ribs — each  in  1  case. 

The  adjacent  structures  were  invaded  by  direct  extension  in  20 
of  these  27  necropsies,  as  follows  : — pelvic  connective  tissue  in  14  cases, 
peritoneum  in  10  cases,  bladder  in  8  cases,  vagina  and  portio  in  5  cases 
(of  12  necropsies  in  females),  omentum  and  pelvic  bones — each  in  1  case. 

The  adjacent  lymph-glands  were  obviously  invaded  in  17  of  21 
necropsies. 

Besides  the  case  in  the  foregoing  series,  in  which  the  disease  dis- 
seminated in  the  dorsal  vertebrae  and  ribs,  I  know  of  several  other  instances 
of  this  kind,  e.g.,  in  the  right  humerus  by  Pitts  1  (with  spontaneous  frac- 
ture) ;  in  both  innominate  bones,  both  tibiae,  eighth,  tenth  and  eleventh 
dorsal  vertebrae,  right  parietal  bone  and  basis  cranii,  as  well  as  in  the 
liver,  one  lung  and  the  intra-abdominal  lymph-glands  by  Gowers  ;  2  in  the 
left  femur,  liver  and  lung  by  Fuzinami  ;  3  and  by  Goetsch4  in  the  sternum, 
first,  second,  and  seventh  ribs,  cranium,  vertebrae  and  right  femur,  as 
well  as  in  the  liver,  lungs,  right  kidney  and  retro-peritoneal  glands. 

Of  1 1  necropsies  for  cancer  of  the  pancreas,  N.  Moore  5  found  meta- 
stases in  7,  or  in  63-6  per  cent.,  the  liver  being  involved  in  6,  the  lungs  and 
kidneys  each  in  2  cases,  the  peritoneum  and  heart  each  in  1  case.  In 
3  cases  adjacent  parts  were  invaded  by  direct  extension,  viz.,  the  stomach, 
gall-bladder  and  transverse  colon  in  1  case,  the  duodenum  in  another, 
portal  fissure  and  its  lymphatics  in  the  third  case. 

In  epithelial  cancer  of  the  ovary  metastases  are  of  very  frequent  occur- 
rence ;  for,  of  my  series  of  9  consecutive  necropsies,  lesions  of  this  kind  were 
noted  in  8,  or  in  88-8  per  cent.,  the  parts  affected  being  the  liver  in  5  cases, 
peritoneum  5  cases,  lung  (right)  in  2  cases,  great  omentum  2  cases  ; 
pleura,  pericardium,  pancreas,  kidney  (left),  intestine,  mamma  (right), 
bladder,  heart,  and  skin — each  in  1  case. 

The  following  parts  were  also  invaded  by  direct  extension  of  the 
disease  :  uterus  in  4  cases  (with  Fallopian  tube  in  2),  peritoneum  in  3 
cases,  rectum,  right  ureter  and  kidney — each  in  1  case. 

Of  4  necropsies  for  malignant  epithelial  tumours  of  the  testis,  Butlin  6 
found  that  metastases  had  taken  place  in  every  case,  as  follows  : — 
(1)  liver,  lungs  and  right  breast ;  (2)  liver  and  lungs  ;  (3)  adrenal  ; 
(4)  omentum. 

1  Transactions  of  the  Pathological  Society,  London,  1891,  vol.  xlii.,  p.  267. 

2  Lancet,  1905,  vol.  ii.,  p.  1593. 

3  Arch.  f.  path.  Anat.,  1897,  Bd.  cxlvii.,  S.  129. 

*  Ziegler's  Beitr.  z.  path.  Anat.,  etc.,  1906,  Bd.  Ixxxix.,  S.  218. 
5  Op.  cit.  6  "  Sarcoma  and  Carcinoma,"  1882. 


438  THE  NATURAL  HISTORY  OF  CANCER 

In  every  case  there  was  dissemination  in  the  adjacent  lymph-glands. 

Of  my  6  necropsies  for  cancer  of  the  bladder,  metastasis  was  noted 
in  only  1 — there  being  a  single,  small,  cancerous  nodule  in  the  right 
lobe  of  the  liver. 

In  3  cases  the  adjacent  parts  were  invaded  by  direct  extension,  viz., 
the  pelvic  connective  tissue  in  2  cases,  and  the  left  ovary  in  1  case. 

S.  Cooper  has  known  this  local  variety  of  cancer  disseminate  in  the 
left  femur  (with  spontaneous  fracture),  and  in  the  fifth  right  rib. 


The  Metastases  of  Sarcomatous  Tumours. 

Of  91  necropsies  for  sarcoma  of  the  female  mamma  tabulated  by 
Gross,1  metastases  were  found  in  17,  or  in  18-68  per  cent.  ;  and  of  40 
similar  cases  by  Schuoler,2  in  12-4  per  cent. 

As  Gross  has  pointed  out,  the  liability  to  metastasis  varies  with  the 
structure  of  the  primary  tumour,  the  percentage  figure  being  25  for  the 
round-celled  variety,  and  20-4  for  the  spindle-celled  ;  while  none  of  the 
myeloid  forms  disseminated. 

In  Gross'  cases  the  metastatic  tumours  were  located  as  follows  : — 
lungs  in  10  cases,  liver  in  4,  brain  in  3  ;  and  1  each  in  the  dura  mater, 
retro-peritoneal  glands,  mediastinum,  pleura,  heart,  kidney,  muscles 
and  bones. 

Of  8  necropsies  for  this  malady  by  Campiche  and  Lazarus-Barlow,3 
metastases  were  noted  in  the  liver  in  4  cases,  pleura  in  3,  kidneys  in  3, 
brain  in  2  ;  and  1  each  in  the  pericardium,  stomach,  intestines,  mesentery, 
sternum,  lungs  and  adrenal. 

In  a  case  recorded  by  Virchow,4  the  disease  disseminated  in  the  lungs, 
liver,  mediastinum,  ribs,  vertebrae,  pelvic  bones,  dura  mater  and  sphenoid. 
Delbarre 5  has  seen  round-celled  mammary  sarcoma,  associated  with 
similar  ovarian  disease. 

Of  8  necropsies  in  my  list,  for  sarcoma  of  the  superior  maxilla — only 
3  of  which  were  myeloid — none  originated  metastases.  In  one  of  these 
cases,  the  disease  had  spread  by  direct  extension,  through  the  sphenoidal 
fissure  into  the  middle  fossa  of  the  skull,  where  it  formed  a  tumour — the 
size  of  a  walnut — which  compressed  the'brain. 

According  to  Gross,6  metastases  are  met  with  in  64  per  cent,  of  all 
necropsies  for  sarcoma  of  the  long  bones,  the  relative  frequency  of  these 
lesions  varying  with  the  kind  of  tumour,  being  greatest  for  the  periosteal 
forms  (100  to  65  per  cent.),  less  for  central  tumours  (33  to  23  per  cent.), 
and  least  of  all  for  the  myeloid  form  (22  per  cent.).  The  site  incidence 
of  metastases  is  shown  by  the  following  analysis  of  30  necropsies,  in 
which  periosteal  forms  predominated  : — lungs  (generally  both)  in  25  cases, 
bones  in  12,  distant  lymph-glands  (chiefly  bronchial)  in  8,  pleura  in  5, 

International  Journal  of  the  Medical  Science*,  1887,  p.  17. 

Corresp.  Bl.  f.  schw.  Aerzte,  1890,  S.  283. 

"  Archives  of  Middlesex  Hospital,"  1905,  vol.  v.,  p.  112. 

Path,  des  Tumeurs,  t.  ii..  p.  360. 

Butt.,  etc.,  de  la  Soc.  Anat.,  1870,  p.  337. 

American  Journal  of  the  Medical  Sciences,  July  and  October,  1879. 


THE  MORPHOLOGY  OF  MALIGNANT  TUMOURS         439 

diaphragm  in  3,  kidney  in  3,  pericardium  in  2,  brain  in  2,  liver  in  2  ; 
omentum,  spleen,  subcutaneous  tissue,  inferior  vena  cava  and  muscles — 
each  in  1  case. 

Of  22  cases  of  sarcoma  of  the  femur,  by  Butlin  and  Colby,1  there  was 
dissemination  in  the  lungs  in  7,  kidney  in  2,  bones  in  2  ;  diaphragm,  ureter, 
and  pleura — each  in  1  case. 

Of  13  cases  of  sarcoma  of  the  tibia  by  the  same  authors,  metastases 
had  formed  in  2 — the  lungs,  ribs,  clavicle,  skull  and  femur  being  invaded 
in  1  case  ;  and,  in  the  other,  the  lungs,  pleura,  pericardium  and  various 
bones. 

Sarcomatous  tumours  of  the  choroid  and  uveal  tract — which  are 
mostly  of  the  melanotic  kind,  and  of  round-  spindle-  or  mixed-cell  type 
— are  exceedingly  prone  to  form  metastases.  Unfortunately,  none  of 
the  extensive  and  elaborate  analyses  that  have  been  published,  enable 
me  to  state  exactly  in  what  proportion  of  fatal  cases  metastases  are  met 
with  ;  but,  from  the  general  tenor  of  these  reports,  it  may  be  inferred 
that  metastases  are  of  almost  invariable  occurrence.  This  is  the  usual 
cause  of  death  after  extirpation  of  the  globe  etc.  ;  for  local  recurrence 
is  comparatively  rare.  Some  idea  of  the  great  frequency  of  metastasis 
may  be  gathered  from  the  fact,  that  of  243  operated  cases  tabulated  by 
Fuchs,2  only  6  per  cent,  were  alive  and  well  four  years  after  the  operation. 
Of  Lawford  and  Collins'  79  operated  cases,  however,  25-3  per  cent,  were 
alive  and  well  three  years  and  upwards  after  extirpation.  A  curious 
feature  about  the  metastatic  recurrence  of  these  choroidal  sarcomata  is, 
that  they  are  just  as  frequent  after  early,  as  after  late  extirpation  of  the 
eye  ;  although  local  recurrence  is  much  rarer,  when  early  operation  is 
resorted  to.  It  is  also  interesting  to  note,  that  the  secondary  tumours 
are  not  invariably  pigmented,  when  the  primary  tumour  is  thus 
characterized.3  As  previously  mentioned,  choroidal  sarcoma  hardly 
ever  disseminates  in  adjacent  lymph-glands.4  It  is  generally  considered 
that  the  soft,  cellular,  and  vascular  forms  of  choroidal  sarcoma,  have  the 
greatest  proclivity  to  disseminate  by  metastasis.  Of  the  parts  thus 
implicated,  the  liver  is  the  one  most  frequently  mentioned  ;  other  parts  apt 
to  be  affected  are  the  kidneys,  stomach,  lungs,  heart,  skin,  bones,  intes- 
tines, muscles,  and  very  rarely  the  serosa,  the  spinal  and  cranial  cavities. 

With  glioma  of  the  eye,  metastases  are  of  very  much  rarer  occurrence, 

1  St.  Bartholomew's  Hospital  Report.  1895,  vol.  xxxi. 

2  Das  Sarcom  des  UveaUractus,  Wien,  1882. 

3  J.  H.  Parsons  has  reported  an  instance  in  which  a  melanotic  sarcoma  of  the  choroid, 
with  an  unpigmented  mtra-ocular  extension,  caused  death   by  metastasis  in  the  liver  one 
and  a  half  years  after  extirpation  of  the  affected   eye,  when  several  ribs,  the  lung  and 
mediastinal  glands,  were  found  to  be  invaded  by  secondary  growths  having  the  structure 
of  squamous-celled  epithelioma  (Lancet,  1904,  vol.  ii.,  p.  1421). 

4  Referring  to  this,  Juler  says  (Handb.  Ophth.  Sci.,  p.  153): — "In  many  cases  the 
tissues  outside  the  sclerotic  are  affected  by  the  new  growth,  while  the  tumour  inside  the 
globe  is  quite  small ;  in  these  cases  the  cells  pass  to  the  outside  by  means  of  the  sheaths 
of  the  bloodvessels,  which  are  seen  to  be  thickened  and  altered  by  the  presence  of  cells 
similar  in  character  to  those  of  the  tumour.  .  .  .  The  neighbouring  lymphatic  glands  are 
not  affected  ;    but  secondary  sarcoma  is  liable  to  be  set  up  in  distant  parts,  the  cells 
being  conducted  from  this  primary  source  by  means  of  the  blood  current."     In  view  of 
the  incongruities  thus  indicated,  is  it  not  more  probable  that  the  tumour-cells  emerge 
from  the  globe,  within  the  bloodvessels,  rather  than  in  their  external  sheaths,  as  the 
appearances  seem  to  indicate  ? 


440  THE  NATURAL  HISTORY  OF  CANCER 

than  with  sarcoma  of  the  choroid  ;  while  lymph-gland  dissemination  is 
commoner.  I  have  seen  glioma  disseminate  in  the  dura  mater,  and  in 
the  right  deltoid  muscle  ;  and  Knapp,1  in  the  liver,  lungs  and  cranial 
bones.  Metastasis  has  also  been  known  to  involve  the  kidney,  ovary, 
sternum  and  ribs.  In  cases  of  this  kind,  Bizzozero  and  others  have 
found  glia  cells  in  the  blood. 

Of  13  necropsies  for  sarcoma  of  the  testis,  in  Butlin's  2  analysis, 
metastases  were.found  in  11,  or  in  84-6  per  cent.,  the  parts  invaded  being 
as  follows  : — lungs  in  7  cases,  bones  in  3,  heart  in  3,  subcutaneous  tissue 
in  2,  kidney  in  2  ;  and  in  the  liver,  skin,  penis  and  spleen — each  in  1  case. 
There  was  lymph-gland  dissemination,  in  11  of  14  fully  examined  cases. 

Of  50  fatal  cases  of  deciduoma  malignum  vel  chorio-epithelioma, 
tabulated  by  me,  metastases  were  found  on  post-mortem  examination 
in  41,  or  in  82  per  cent.  ;  the  percentage  site  incidence  was  as  follows  : — 
the  lungs  in  72,  brain  20,  kidney  18,  spleen  16,  liver  14,  intestine  12, 
heart  10 ;  mesentery,  bronchial  glands,  bones  and  stomach — each  in 
4  per  cent.  ;  pancreas,  pulmonary  and  hepatic  veins,  omentum  and 
thyroid — each  in  2  per  cent. 

The  following  adjacent  structures  were  also  involved  : — vagina  in 
44  per  cent.  ;  other  parts  of  the  uterus  than  that  occupied  by  the  primary 
focus,  in  20 ;  one  or  both  ovaries,  in  14 ;  peritoneum,  in  12  ;  both  broad 
ligaments,  in  8  ;  pelvic  connective  tissue,  in  4  ;  bladder  and  abdominal 
wall — each  in  2  per  cent. 

In  these  same  cases  there  was  dissemination  in  the  adjacent  lymph - 
glands,  only  in  5  cases,  or  in  10  per  cent. 

Thus  this  anomalous  form  of  malignant  tumour  in  its  metastases,  as 
in  its  lymph-gland  dissemination,  manifests  more  similitude  to  sarcoma 
than  to  epithelioma. 

General  Conclusions. 

Reviewing  the  whole  subject  in  the  light  of  the  foregoing  facts,  it 
appears  that  all  kinds  of  dissemination — local,  glandular  and  metastatic 
— are  of  less  frequent  occurrence  with  sarcomatous,  than  with  malignant 
epithelial  tumours  ;  this  peculiarity  being  most  marked  in  respect  to 
lymph-gland  dissemination.  The  alleged  frequency  of  lymph-gland 
dissemination  with  sarcoma  of  the  tonsil  and  testis,  is  not  based  on  a 
sufficiently  large  number  of  duly  authenticated  cases,  to  rank  as  an 
ascertained  fact.  As  for  the  other  apparent  exception  to  this  rule, 
melanotic  sarcoma  of  the  skin,  most  pathologists  now  consider  the 
majority  of  these  tumours,  to  be  of  epithelial  origin. 

Myeloid  sarcoma,  like  rodent  ulcer,  seldom  originates  any  kind  of 
disseminative  lesion. 

The  only  other  epitheliomatous  tumour,  with  which  lymph-gland 
dissemination  is  not  of  frequent  occurrence,  is  the  so-called  "  chorio- 
epithelioma  " — the  affinity  of  which  with  sarcoma,  is  clearly  indicated 
by  all  its  disseminative  manifestations.  In  this  form  of  malignant 
disease,  as  in  periosteal  sarcoma  of  the  long  bones,  metastatic  dissemina- 
tion is  of  the  greatest  frequency. 

1  Die  intraocularen  Oeschunilste,  1868.  2  Op.  cit. 


THE  MORPHOLOGY  OF  MALIGNANT  TUMOURS         441 

Another  important  feature  indicated  by  our  analysis  of  the  data  of 
dissemination  is,  that  for  all  epithelial  malignant  tumours,  the  liver  is     x 
the  organ  most  frequently  the  seat   of  the  metastasis  ;   whereas,   for 
sarcomata,  the  lung  is  the  commonest  seat  of  these  lesions. 

With  regard  to  the  malignant  epithelial  tumours,  the  only  apparent 
exception  to  this  rule  is  in  the  case  of  thyroid  ;  but,  thyroid  sarcomata 
often  comprise  epithelial  elements,  blended  in  such  a  way  as  to  make 
the  discrimination  from  epithelioma  by  histological  examination  prac- 
tically impossible,  as  I  have  previously  mentioned.  Owing  to  this  cause, 
no  doubt  many  adeno-sarcomata  have  been  classed  in  Ehrhardt's  tables," 
as  epitheliomata.  This  is  but  another  example  of  the  importance  of 
metastatic  manifestations,  as  an  element  in  the  problem  of  the  diagnosis 
of  the  type  of  malignancy,  for  which  the  histological  appearances  per  se 
are  so  often  inadequate. 

In  the  case  of  sarcomata,  the  only  apparent  exception  to  our  rule  of 
the  lung  being  the  commonest  seat  of  metastasis,  is  to  be  found  in  the 
choroid,  where  the  liver  is  generally  credited  with  this  distinction  ;  but,  , 
as  to  this,  there  is  at  present  lack  of  precise  numerical  details.  Besides, 
is  it  absolutely  certain — in  view  of  Parsons'  previously  cited  case,  and  of 
other  indications  of  similar  import — that  all  melanotic  choroidal  malig- 
nant tumours,  are  of  connective-tissue  origin  I1 

With  regard  to  intra-osseous  metastases,  although  both  types  of 
malignant  disease  not  infrequently  cause  them,  there  can  be  no  doubt 
that  they  are  of  commoner  occurrence  with  the  epithelial  type  of  tumour, 
than  with  its  connective-tissue  counterpart.  With  the  latter  type  of 
malignant  disease  this  form  of  metastasis  is  most  frequent,  when  the 
primary  localization  is  skeletal ;  and,  even  with  epithelial  cancer,  the 
commonest  precursor  of  intra-osseous  dissemination  often  is  the  invasion 
of  some  bone  adjacent  to  the  primary  cancer,  by  direct  extension  of  the 
latter,  such  for  instance,  as  the  sternum,  ribs,  clavicle  or  upper  end  of 
the  humerus,  when  the  breast  is  the  original  seat  of  the  disease. 

As  may  be  gathered  from  what  has  already  been  stated,  recent 
experience  shows  that  dissemination  in  the  bones  is  of  much  more  fre- 
quent occurrence  than  has  hitherto  been  supposed,  several  of  those  who 
have  specially  examined  the  subject  having  found  intra-osseous  metas- 
tases in  from  20  to  25  per  cent,  of  all  cancer  necropsies  (E.  Fraenkel, 
Fischer-Defoy  etc.).  Intra-osseous  lesions  of  this  kind  comparatively 
seldom  cause  obvious  external  deformity  ;  hence,  unless  the  skeleton  is 
specially  examined  ad  hoc,  such  lesions  usually  escape  notice.  No  cancer 
necropsy  ought  to  be  considered  as  complete,  without  special  examination  "/ 
of  the  skeleton. 

Some  remarkable  differences  in  the  proclivity  of  malignant  tumours 
of  particular  localities  to  disseminate  in  the  bones  are  noticeable.  I 
have  already  referred  to  the  great  frequency  of  such  occurrences  when 
the  primary  disease  is  situated  in  the  prostate,  thyroid,  mamma  and 
skeletal  bones  ;  and  to  its  decided  rarity  when  the  initial  lesion  is  of 
cutaneous,  labial,  buccal.  lingual,  intra-ocular,  uterine  or  gastric  origin  ; 

1  For  some  pertinent  remarks  on  this  subject  by  Lawford,  vide  British  Medical  Journal, 
1892,  vol.  ii.,  p.  84. 


442  THE  NATURAL  HISTORY  OF  CANCER 

while,  when  the  rectum  or  oesophagus  is  the  part  affected,  intra-osseous 
dissemination  is  not  of  such  exceptional  rarity. 

Lately  Scudder  l  has  called  attention  to  the  frequency  with  which  a 
certain  type  of  renal  malignant  tumour  (hyper-nephroma)  disseminates 
in  the  bones  ;  and  R.  Hutchison  2  has  collected  many  instances  of  this  kind 
secondary  to  supra-renal  "  sarcoma  "  of  early  life. 


The  Theory  of  Metastasis. 

By  far  the  most  feasible  explanation  known  to  me  of  the  phenomena 
of  metastasis,  is  that  furnished  by  the  "  embolic  theory."  This  implies 
that  the  germs  whence  metastases  arise  are  proliferous  cells,  detached 
from  the  primary  neoplasm,  or  its  derivatives.;  and  carried  off  by  the 
blood-stream.  These,  by  their  continuous  proliferation,  directly  originate 
the  secondary  growths  ;  so  that  the  first  cancer  is  the  parent  of  all  that 
form  after  it.  The  conception  of  metastasis,  as  due  to  specific  virus 
(blastema  etc.)  dissolved  in  the  blood,  belongs  to  old  humoral  pathology  ; 
and  now  finds  no  support,  except  with  those  who  would  revive  the  old 
doctrine,  in  connexion  with  the  microbic  theory. 

According  to  Nepveu,3  the  veritable  agents  of  dissemination,  are  not 
the  cancer  cells  themselves — for  these  are  generally  too  large  to  pass 
through  the  capillaries  —  but  their  young  offspring  (seminium  cellu- 
laire),  which  penetrate  everywhere.  These  minute  bodies  he  claims 
to  have  found  in  the  blood  of  the  tumour  and  its  vicinity,  as  well  as  in 
the  general  circulation. 

It  accords  with  this  conclusion,  that  the  only  structures  in  which 
metastases  are  never  found,  are  avascular  parts,  like  cartilage  and 
cornea,  which  are  permeable  to  fluids,  but  not  to  cells. 

Friedreich's  4  case  of  cancerous  dissemination  in  the  skin  over  the  left 
knee  of  a  foetus— whose  mother  died  during  pregnancy  with  cancer  of 
the  liver,  and  multiple  disseminative  nodules  in  the  uterus,  mammae, 
bones,  intestines  etc. — much  relied  upon  by  the  advocates  of  infection  by 
the  fluids,  as  supporting  their  theory,  can  be  accounted  for  by  the  embolic 
theory.  We  know  from  Porak's  researches,  that  foreign  substances  may 
pass  through  the  placenta,  although  as  a  rule  there  is  no  mixing  of  foetal 
and  maternal  blood.  The  permeability  of  the  placenta  to  microbes,  has 
also  been  demonstrated.  Hence  we  may  infer  that  young  cancer  cells, 
which  often  are  exceedingly  minute,  may  also  pass  through  the  placenta. 

In  the  first  chapter  of  this  work,  I  indicated  that  each  of  the  con- 
stituent phenomena  of  malignancy — including  metastasis — has  its 
physiological  prototype.  Before  proceeding  further  with  the  develop- 
ment of  our  rationale  of  metastasis,  it  seems  desirable  here  to  discuss 
briefly  its  physiological  prototype. 

1  "Publications  of  Massachusetts  General   Hospital,"   Boston,   U.S.,   1907,  vol.  i., 
-\"o.  3,  p.  82. 

2  Quarterly  Journal  of  Medicine,  1907,  vol.  i.,  No.  1. 
Aev.  des  Maladies  Cancereuses,  October  20,  1895,  p.  7. 

4  Arch.  f.  path.  Anat.,  Bd.  xxxvi.,  S.  465. 


THE  MORPHOLOGY  OF  MALIGNANT  TUMOURS          443 

It  is  a  curious  fact,  that  in  the  phases  of  placentation,  all  the  pheno- 
mena of  malignancy  find  their  counterparts.  Pathologists  have  often 
remarked  on  the  similarity  between  the  early  stages  of  placenta  forma- 
tion — when  the  maternal  tissues  are  invaded  and  interpenetrated  by 
foreign  epithelial  ingrowths — and  the  cancerous  process  ;  and,  by  some, 
the  placenta  itself  has  been  regarded  as  a  kind  of  "  physiological  tumour." 
Under  normal  circumstances,  these  infiltrating  processes,  are,  of  course, 
confined  within  strict  limits  ;  and  this  it  is  which  constitutes  the  dis- 
tinction from  malignancy. 

As  long  ago  as  1893,  Schmorl x  found  that  portions  of  the  chorionic 
villi  and  cellular  fragments  thereof,  were  freely  shed  into  the  maternal 
circulation  in  puerperal  eclampsia  ;  and,  in  1901,  Veit 2  and  others  showed 
that  similar  occurrences  are  usual  in  the  majority  of  normal  pregnancies. 
These  "  deported  "  elements  have  great  power  of  wandering  ;  and,  by 
their  own  vitality,  are  capable  of  penetrating  the  maternal  bloodvessels 
and  lymph-spaces.  'Usually,  however,  such  emigrants  are  soon  dissolved 
by  the  maternal  blood,  and  completely  disappear. 

But,  under  certain  abnormal  circumstances,  as  yet  not  fully  under- 
stood, these  "  deported  "  chorionic  elements — instead  of  being  absorbed 
— grow  into  tumour-like  formations,  of  malignant  or  non-malignant 
character,  according  to  the  dynamical  qualities  elicited,  The  kind  of 
foetal  lesion  which  specially  predisposes  to  this  disease,  ig  the  hydatidi-  , 
form  mole,  now  generally  regarded  as  a  chorionic  tumour,  with  malignant 
and  non-malignant  varieties.  It  seems  possible,  however,  that  these 
chorionic  tumours  inay  exceptionally  arise,  even  in  the  absence  of  any 
recognizable,  primary  neoplastic  focus  in  the  chorion,,or  elsewhere ; 
however  tin's  may  be,  it_is_a_jcertain_fact.  that  more  than  half  of  those 
with  chorionic  tumours,  have  been  the  subjects  of  previous  "  mole " 
pregnancy.  Just  as  it  is  impossible  to  draw  a  sharp  line  of  distinction 
between  the  malignant  and  non-malignant  varieties  of  "  mole.";  so 
likewise  it  is  impossible  to  draw  any  such  distinction  between  the  benign 
and  malignant  varieties  of  "  chorioma," 

Now  the  question  arises,  Jigw  is  it  th-at  these  "  deported  "  chorionic 
elements,  survive  and  grow  into  tumours  injsome  cases,  while  in  others 
they  are  completely  absorbed  ?,  The  indications  at  present  available, 
especially  the  almost  invariable  occurrence  of  these  tumours  post-partum 
• — after  abortion,  "  mole  "  pregnancy,  or  other  processes  involving  death 
orjremoval  of  the  foetus— all  point  to  abnormal  changes  in  the  ovary,  as 
the  determining  factor,,  of  which  we  have  evidence  in  the  frequent  con- 
currence of  cystic  disease  of  the  ovaries,. with  hydatidiform  mole  and  with 
malignant  chorionic  tumours. 

Owing  to  alterations  of  this  kind  and  to  the  changes  in  the  blood, 
which  they  induce,  the  latter  loses  its  normal  power  of  dissolving,  the 
intruding  chorionic  cells  (syncytiolysis)  ;  which,  under  these  pathological 
circumstances,  then  acquire   powers   of   abnormal    growth,  the  various 
chorionic  tumours  being  the  consequence. 

It  is  thus  probable,   that  some   alteration  of   the  ovarian  internal 

1  Verschleppung  der  Choriozotten,  Leipzig,  1893. 

2  Zeitschr.  f.  Geb.  u.  Oyn.,  Bd.  xliv.,  S.  466. 


444  THE  NATURAL  HISTORY  OF  CANCER 

secretion,  is  the  dominant  factor  underlying  the  various  pathological 
changes  of  which  jnetastagis  is  the  outcome  ;  and,  hence,  may  we  infer 
that  some  such  change  in  the  internal  secretion  of  the  sexual  glands — and 
even  of  other  organs— plays  a  part  in  the  determination  of  metastasis  in. 
general  ? 

This  conclusion  certainly  harmonizes  with  other  indications  to  which 
L  have  previously  referred,  such  as  the  frequency  of  malignant  disease 
in  castrated  animals,  and— in  humanity — after  the  surgical  removal  of 
the  ovaries,  or  in  consequence  oi  their  impairment  by  disease  x>r  by  con-^ 
genital  defect ;  and  a  similar  indication  is  the  coincidence-  of  the  greatest 
proclivity  to  cancer,  with  decline  of  reproductive  activity,  to  which  I 
have  specially  directed  attention  in  a  previous  chapter.1 

Whether  this  is  the  correct  explanation  of  metastasis  in  general  or 
not,  the  site-incidence  of  these  formations  and  other  phenomena  of 
similar  import,  clearly  indicate  ;  that  the  formation  of  metastases,  is 
ppnditioned  by_  other,  considerations,  besides  those  of  mere  mechanical 
distribution. 

Many  observations  indicate  that  cancer  cells  enter  the  blood-stream 
directly,  through  the  bloodvessels— especially  the  small  veins-— as  well 
as  indirectly,  through  the  lymphatics,  Goldmann's  2  researches  being  of 
special  significance  in  this  connexion. 

Here  also  we  must  bear  in  mind,  as  has  lately  been  redemonstrated, 
that  there  are  many  direct  communications  between  the  lymphatics 
and  venous  radicles,  through  which  the  diseased  cells  may  readily  dis- 
seminate from  the  one  to  the  other  system  (Leaf,  Warthin — "  hsemo- 
lymph  glands  "  etc.)  by  a  kind  of  short  circuiting ;  and  thus  may 
be  explained  many  apparent  anomalies,  in  the  site-incidence  of 
metastases. 

The  occurrence  of  metastasis,  without  any  lymph-gland  dissemina- 
tion, which  is  usual  with  sarcoma,  and  less  frequent  with  malignant 
epithelial  tumours,  is  evidence  of  this ;  and  my  own  belief  is  that,  even 
with  cancers  of  the  epithelial  type,  metastasis  often  originates  in  this 
way.  Thus,  hardly  ever  can  a jnalignant  epithelial  tumour  of  the  mamma 
be  examined,  without  finding  its  veins,  and  those  of  its  vicinity,  invaded 
by  the  disease.  In  the  earliest  stage,  the  venous  wall  becomes  adherent 
to  the  neoplasm  ;  then  it  gets  infiltrated,  and  its  external  coat  per- 
forated.3 In  the  next  stage,  the  new  growth  projects  more  and  more 
into  the  vein,  covered  only  by  the  intima  of  the  latter.  This  soon  yields, 
and  the  neoplasm — in  the  form  of  a  small  fungus — then  projects  into 
the  lumen  ;  whence  the  growth  may  be  detached  en  masse,  or  in  minute 
fragments.  Cancer  emboli  of  this  kind  have  frequently  been  found  fiee 
in  the  blood,  between  the  primary  seat  of  disease  and  its  derivatives, 
and  the  right  side  of  the  heart ;  and,  even  in  the  latter,  and  in  the  pul- 
monary artery — its  main  trunk  and  its  smaller  branches.  A  remarkable 
feature  lately  brought  to  light  by  the  researches  of  Goldmann  and  Schmidt^ 

1  Chapter  XV. 

2  E.g.,  Goldmann  (Deutsche  med.    Woch.,  1906,  No.  41):  also  Lancet,  1907,  vol.  ii., 
p.  1237,  etc. 

3  According  to  Goldmann,  the  tumour  cells  reach  the  wall  of  the  vessel  by  way  of 
the  vasa  vasorum. 


THE  MORPHOLOGY  OF  MALIGNANT  TUMOURS          445 

is,  that  although  the  blood-stream,  may  teem  with  cancer  cells,  there 
may  be  no  evidence  of  metastatic  tumour  formation. 

M,  B.  Schmidt's  work  1  on  the  dissemination  of  malignant  epithelial 
tumours,  is  a  convincing  demonstration  of  the  spread  of  cancer  elements 
by  the  blood-stream  -r  thus,  in  IS^pf^l^cases  examined,  he  found  emboli, 
composed  of  cancer  cells,  in  the  smaller  branches  of  the  pulmonary 
arteries T  although  only  a  small  proportion  of  these  eventually  developed 
into  cancerous  tumours. »- 

Similarly  Councilman  has  shown,  by  careful  examination  of  very, 
minute  secondary  growths  in  the  liver,  originating  from  primary  foci 
within  the  portal  area,  that  these  are  at  first  situated,  entirely  within  the 
portal  capillaries.  Many  other  observations  of  similar  import  might 
easily  be  cited  ^  thus,  Goldmann2  has  specially  shown  how  frequently 
the  small  veins  of  cancerous  tumours  are  invaded,,  and  he  has  found 
cancer  cells  free  in  the  blood,  as  well  as  in  intra- venous  clots,  and  in  the 
venous  walls.  In  exceptional  cases,  even  the  arteries  may  be  thus 
invaded  ;  and,  in  this  way,  sudden  and  extensive  dissemination  of  the 
disease  may,,  he  believes,  be  brought  about. 

It  is  certainly  a  mistake  to  suppose,  that  when  free  cancer  cells  enter 
the  circulation,  they  necessarily  or  usually  cause  clotting.;  and  also  that 
cancer  cells  are  unable  to  grow  in  blood-clot. 

Loeb's  remarkable  experiments  as  to  the  cancer-like  growth  of  epi- 
thelium in  blood-serum  and  agar^  as  well  as  many  other  pathological 
observations  to  the  like  effect,  contradict  the  latter  ;  while  the  presence 
of  cancer  cells  in  the  circulation,  and  of  cancerous  formations  in  intra- 
vascular  blood-clots,  as  noted  by  many  observers,  likewise  contradict  the 
former. 

Then,  how  can  we  account  for  epidermoidal-celled  cancer  of  the  tongue, 
producing  an  epidermoidal-celled  cancerous  metastasis  in  the  left  adrenal, 
with  no  other  general  disseminative  lesion,  as  described  in  a  previously 
cited  case  by  Arnott,  except  by  the  embolic  theory  ? 

Examples  of  this  kind  may  be  multiplied  almost  indefinitely,  e.g.,  epi- 
dermoidal  cancer  of  the  skin  of  a  limb,  with  epidermoidal  cancer  of  the 
glottis,  as  reported  by  Chapuis  ;  3  epithelial  cancer  of  the  bladder,,  with  a 
single  metastatic  nodule  of  similar  structure  in  the  right  lobe  of  the 
liver,  and  no  other  general  disseminative  lesion,  as  in  a  case  I  have 
seen  etc. 

Similarly,  how  can  we  account  for  metastatic  cancer  of  the  choroid 
of  the  eye,  secondary  to  mammary  cancer. — of  which  over  a  score  of 
cases  have  lately  been  reported — except  by  the  embolic  theory  ? 

And,  is  it  not  just  the  same,  with  such  cases  as  that  described  by 
Schaper,4  in  which  primary  cancer  of  the  lung  disseminated  in  an  intersti- 
tial uterine  myoma  ;  and  as  that  by  Bender  and  Lardennois,5  in  which 
primary  cancer  of  the  female  breast  likewise  disseminated  in  a  uterine 
myoma — no  other  part  of  the  uterus  being  invaded  ;  as  well  as  in 

"  Die  Verbreitungswege  der'Karzinome,"  etc.    Jena,  1903. 

Op.  cit.  ;  and  Berlin  klin.  Woch.,  June  15,  1896,  S.  549. 

Lyon.  Med.,  March  1,  1896. 

Arch.  f.  path.  Anat.,  1892,  Bd.  cxxix.,  S.  61. 

Butt,  et  mem.  de  la  Soc.  Anat.,  Paris,  October,  1904. 


446  THE  NATURAL  HISTORY  OF  CANCER 

Friedreich's  *  case  of  metastasis  in  the  left  knee  of  a  foetus,  whose 
mother  died  of  cancer  of  the  liver  with  metastases,  during  pregnancy. 

Recklinghausen's  2  careful  study  of  the  minute  anatomy  of  the  mtra- 
osseous  dissemination  of  cancer,  secondary  to  primary  foci  in  the  prostate, 
thyroid  etc.,  is  of  similar  import ;  for  in  all  these  intra-osseous  lesions  he 
was  able  to  demonstrate,  that  the  disease  originated  and  spread  in  the 
medullary  bloodvessels,  where  the  circulation  is  comparatively  slow. 

Then,  with  regard  to  "  chorioma  malignum,"  do  we  not  constantly  find 
secondary  growths  loose  within,  the  veins u?f  , the  uterus,  vagina  and 
adjacent  parts  ;  as  well  as  in  theJems  of  the  fungsfbrain,  the  large  veins  in 
the  vicinity  of  the  heart,  the  venacava  inferior,  the  pulmonary  artery  and 
its  ramifications  in  the  lungs,  and  even  in  the  cavities  of  the  heart  itself  ? 

To  my  mind  all  these  occurrences  and  many  others  of  similar  import, 
which  are  constantly  presenting  themselves  in  connexion  with  the 
metastasis  of  cancer,  are  absolutely  inexplicable  without  the  aid  of  the 
embolic  theory.  Certainly,  it  is  quite  impossible  to  explain  such  occur- 
rences on  the  basis  of  "  lymphatic  permeation  "  ;  which,  for  this  reason, 
must  be  regarded  as  a  far  inferior  working  hypothesis  to  the  embolic 
theory  for  interpreting  the  facts  of  metastasis. 

We  have  now  to  inquire,  what  it  is  that  determines  the  development 
of  metastatic  tumours,  in  certain  localities,  rather  than  in  others. 
There  can  be  no  doubt  that  the  dissemination  of  cancer  emboli  is  regulated 
by  the  same  mechanical  conditions,  which  determine  the  distribution  of 
ordinary  emboli  :  from  the  veins  at  the  root  of  the  neck,  they  pass  to  the 
right  side  of  the  heart,  and  thence  to  the  lungs  ;  whence  those  small 
enough  pass  through  the  pulmonary  capillaries,  and  so  into  the  left  side 
of  the  heart,  and  thence  into  the  aortic  system.  It  seems  to  follow  from 
this — since  the  pulmonary  capillaries  are  considerably  smaller  than  most 
cancer  cells — that  the  latter  must  generally  be  arrested  first  of  all  in  the 
lungs  ;  and  this  is  just  what  the  researches  of  Martin  Schmidt  3  show 
actually  takes  place.  Thus,  of  twenty-eight  cases  of  metastasis  investi- 
gated by  him,  in  all  of  which  the  primary  morbid  focus  was  outside  the 
portal  system,  epithelial  cancer  elements  derived  from  this  focus  were 
found  in  the  lungs  in  every  case.  He  was  able  to  determine  that  in 
thirteen  cases  these  lesions  were  due  to  lymphatic  dissemination,  through 
the  diaphragm  to  the  pleura,  by  retrograde  conveyance  from  affected 
bronchial  glands  etc.  In  all  the  other  fifteen  cases,  emboli  containing 
cancer  cells  were  found  in  the  smaller  branches  of  the  pulmonary  arteries 
in  the  lungs.  But,  as  we  have  already  seen  as  the  result  of  our  post- 
mortem analyses,  and  as  ^Schmidt's  researches  also  show,  cancerous 
metastases  form  in  the  lungs  much  less  frequently  than  these  emboli 
were  found  in  them  ;  hence  it  is  evident,  as  Schmidt  specially  points  out. 
that  most  of  these  cancerous  emboli  perish  and  are  absorbed,  failing  to 
find  in  the  lungs  conditions  favourable  to  their  continued  growth.  Prob- 
ably most  of  them,  owing  to  antecedent  degenerative  changes,  reach 
their  destination  more  dead  than  alive.  Thus,. but  few  of  these  emigrant 
cancer  cells  survive,  so  as  to  originate  secondary  cancerous  growths. 

1  Arch.  f.  path.  Anat.,  Bd.  xxxvi.,  S.  465. 

2  Festschr.  zu  Virchows  71  Geburtstag.     Berlin,  1891.  3  Op.  cit. 


THE  MORPHOLOGY  OF  MALIGNANT  TUMOURS          447 

When  the  initial  morbid  growth  is  of  a  sarcomatous  nature,  say  a 
periosteal  round-celled  sarcoma  of  a  long  bone,  no  doubt  the  mechanism 
of  lung  metastasis  is  identical  with  the  foregoing  ;  but,  in  this  case,  the 
malignant  connective-tissue  cells — being  differently  constituted  to  their 
epithelial  congeners — find  in  the  pulmonary  tissues  a  congenial  habitat, 
in  which  they  readily  continue  their  morbid  growth  ;  so  that  secondary 
sarcomatous  tumours  frequently  form,  although  in  this  case,  as  in  the 
former,  many  of  the  emigrant  cells  certainly  perish  through  degenera- 
tion. 

Thus  may  the  remarkable  difference  in  the  proclivity  manifested  by 
epithelial  and  connective-tissue  malignant  tumours,  to  form  metastases 
in  the  lungs,  be  accounted  for. 

Hence  I  conclude  that  the  diversities  in  the  site-incidence  of  meta- 
static  tumours,  are  not  due  to  the  cancer  emboli  being  arrested  only  in 
certain  selected  situations  ;  but  rather,  that  all  parts  are  exposed  to  their 
incidence  in  accordance  with  the  ordinary  laws  of  embolic  distribution, 
secondary  growths  forming  only  in  those  localities,  where  they  find  . 
suitable  conditions.  Thus,  the  differences  in  the  site-incidence  of  metas- 
tases in  sarcoma  and  epithelioma,  in  respect  of  the  lungs,  are  not  due  to 
diversities  in  the  distribution  of,  the  cancer  emboli ;  but  to  the  fact  that, 
in  the  epithelial  type  of  malignant  disease,  the  arrested  emboli  compara- 
tively seldom  grow  into  secondary  tumours. 

Similarly  may  be  explained  the  great  proclivity  of  malignant  epithelial 
^tumours  to  form  metastases  in  the  liver,  and  the  comparative  rarity  with 
which  sarcomata  disseminate  in  this  organ  ;  as  well  as  the  other  diversities 
of  site  -  incidence  noticeable,  between  the  metastases  of  malignant 
epithelial  and  sarcomatous  tumours. 

In  like  manner  may  also  be  interpreted  the  equally  striking  diver- 
sities, as  to  the  site-incidence  of  metastasesy  between  malignant  tumours 
of  the  same  type,  of  which  our  post-mortem  analyses  furnish  so  many 
examples  ;  such  as  the  frequency  of  metastases  in  the  liver,  secondary  to 
epithelial  cancer  of  the  mamma,  and  the  rarity  of  such  disseminativr 
growths  in  the  spleen,  although  both  organs  are  about  equally  exposed  to 
the  incidence  of  cancer  emboli.1 

Here  also  reference  may  be  made  to  the  singular  immunity  of  the 
muscles  of  the  body  and  some  other  structures  from  metastatic  growths,* 
whether  secondary  to  a  malignant  focus  of  epithelial  or  connective-tissue 
origin  ;  whence  it  may  be  inferred,  that  these  tissues  produce  ..substance* 
inimical  to  the  growth  of  aberrant  cancer  cells  in  their  midst. 

That  cancer  emboli  frequently  survive  and  develop  into  secondary 
tumours,  in  spite  of  the  resistance  of  the  tissues,  evidently  must  be  due 
to  their  abnormal  inherent  activity,  or  to  falling  off  in  the  physiological 
capacity  for  resistance  of  the  tissues  ;  and,  in  most  cases,  it  seems  certain 
that  both  of  these  factors  are  concerned. 

From  the  foregoing  it  will  be  gathered,  that  the  ultimate  fate  of  a 
cancer  embolus — its  complete  absorption  or  its  development  into  a 
secondary  cancerous  growth — depends  mainly  upon  whether  the  inherent 

1  Some  of  this  diversity  is  no  doubt  due  to  direct  extension  of  the  mammary  di 
to  the  liver,  as  Handley  has  indicated. 


448  THE  NATURAL  HISTORY  OF  CANCER 

vital  activity  of  its  constituent  cells,  is  strong  enough  to  resist  successfully 
the  disintegrating  action  of  the  part  of  the  body  in  which  it  has  lodged, 
or  not. 

The  Varieties  of  Cancer. 

The  varieties  of  cancerous  disease  likely  to  arise  in  any  particular 
part  of  the  body,  are  determined  mainly  by  local  structural  peculiarities, 
as  I  have  previously  mentioned  ;  the  history  of  these,  therefore,  properly 
belongs  to  that  of  the  local  forms  of  cancer. 

But  all  cancers  may  manifest  acute  and  chronic  variations,  which  are 
of  great  clinical  importance  ;  and  these  are  the  varieties  to  which  I  here 
propose  to  limit  my  remarks. 

Acute  cancers  are  those  in  which  the  average  course  of  the  malady, 
for  the  special  locality,  is  markedly  abridged  ;  while,  in  chronic  cancers, 
its  duration  is  prolonged  far  beyond  the  average. 

By  way  of  illustrating  the  chief  features  of  each  of  these  varieties  of 
cancer,  it  seems  desirable  to  study  specific  examples  thereof  in  typical 
localities,  such  as  the  mamma  and  uterus. 

Mamma. — Although  epithelial  cancer  of  the  breast  is  usually  a  chronic 
disease — the  average  duration  of  life  according  to  my  calculation  1  being 
-  from  four  to  five  years — yet  certain  cases  occasionally  run  a  very  acute 
course.  Of  these  the  following  types  may  be  recognized  : 

1.  A  very  rare  diffuse  form — denominated  by  the  French  cancer 
cFemblee,  squirrhe  ligneux  en  masse  by  Velpeau,  and  mastitis  carcinoma- 
tosa  by  Klotz — in  which  the  whole  of  one  or  both  breasts  may  be  at  once 
involved.  It  arises  suddenly,  progresses  rapidly,  and  is  often  accom- 
panied by  inflammatory  phenomena.  No  special  tumour  is  formed,  but 
the  whole  breast  becomes  enlarged  and  hard,  the  skin  reddened, 
cedematous  and  adherent,  and  the  subcutaneous  veins  unduly  visible. 
Verneuil  and  Estlander  found  the  temperature  of  the  affected  skin  from 
X  \°  to  2°  above  the  normal ;  and  the  former  has  demonstrated,  in  some 
cases,  a  veritable  cancerous  fever. 

The  adjacent  lymph-glands  are  usually  soon  invaded,  and  there  is 
general  dissemination  of  the  disease,  with  death  from  acute  cachexia. 
Its  total  duration  seldom  exceeds  a  few  months  ;  and  instances  have  been 
reported  by  Billroth  and  Aitken,  in  which  it  proved  fatal  within  six  weeks. 
Most  cases — but  not  all — arise  in  connexion  with  pregnancy  or  lactation  ; 
under  these  circumstances  the  disease  is  apt  to  be  mistaken  at  first  for 
acute  mastitis. 

Examples  of  this  type  of  acute  cancer  have  been  reported  by  Darey,2 
Terrillon,3  Kautorowicz,4  Monod,5  Billroth,6  Aitken,7  Volkmann8  and 
others. 

"  Diseases  of  the  Breast,"  1894,  p.  366. 

Middlesex  HospitalJournal,  1899,  vol.  iii.,  No.  1. 

Butt.  Gin.  de  Therap.,  May  13,  1891,  p.  385. 

Cent.  f.  path.  Anat.,  1893,  Bd.  iv.,  S.  1817. 

Gaz.  Med.  de  Paris,  1886,  pp.  1,  17,  37,  and  48. 

Deutsche  Chir.  Lief.,  xli.,  S.  128. 

Medical  Times  and  Gazette,  1857,  vol.  i.,  p.  357. 

"  "Cher  Mastitis  carcinomatosa  gravidarum  et  lactantium."   Inaug.  Diss.,  Halle,  1869. 


THE  MORPHOLOGY  OF  MALIGNANT  TUMOURS         449 

2.  Although  I  do  not  regard  the  squirrhe  tegumentaire  of  Velpeau  as  a 
distinct  variety,  but  merely  as  a  peculiar  form  of  subcutaneous  dissemina- 
tion of  ordinary  acinous  cancer,  yet  it  will  be  convenient  to  describe  it 
here.  Acinous  cancers,  that  originate  beneath  the  nipple  and  areola,  are 
specially  prone  to  be  followed  by  acute  dissemination  in  the  subcutaneous 
tissue,  owing  to  early  implication  of  the  subareolar  lymphatic  plexus, 
and  rapid  diffusion  of  cancer  cells  through  its  communicating  cutaneous 
branches.  Lesions  thus  induced  assume  the  form  either  of  small  tubercles 
(squirrhe  dissemine,  acute  miliary  carcinosis),  of  irregularly  shaped  discs 
(en  plaques),  or  of  diffuse  infiltrations  (en  cuirasse).  Velpeau,  who  first 
clearly  differentiated  these  conditions,  thought  that  some  cases  were 
from  first  to  last  limited  entirely  to  the  skin  ;  but  most  pathologists  are 
now  agreed  that  the  subcutaneous  infiltration  is  invariably  secondary  to- 
primary  disease  of  the  breast.  Cases  of  this  type  run  a  rapid  course,  and 
are  exceedingly  malignant. 

According  to  Estlander,  the  average  duration  of  life  seldom  exceeds 
from  five  to  twelve  months.  This  estimate  is  no  doubt  true,  for  those 
cases  in  which  the  skin  is  implicated  at  an  early  stage  of  the  disease  ; 
but  I  have  seen  instances,  in  which  this  kind  of  dissemination  did  not 
supervene,  until  several  years  after  the  onset  of  the  primary  disease  in 
the  breast. 

Of  170  cases  of  mammary  cancer  consecutively  under  my  observation, 
there  were  only  2  instances  of  squirrhe  dessemine  ;  and  but  3  of  the 
cuirassed  form  of  the  disease.  According  to  Gross,  this  latter  form  of 
the  malady  is  met  with  once  in  every  22  cases. 

3,.  Lastly,  I  have  to  call  attention  to  certain  cases  of  mammary  cancer 
which — although  they  in  no  way  differ  morphologically  from  ordinary 
acinous  cancers — nevertheless  run  a  very  acute  course.  I  have  met  with 
6  such  cases  out  of  64  consecutive  fatal  breast  cancers.  Nunn l  has 
also  reported  a  case  of  this  kind. 

Mammary  cancers  that  take  more  than  five  years  to  run  their  entire 
course,  I  reckon  as  of  the  chronic  variety.  Such  cases  are  much  commoner 
than  is  generally  supposed  ;  and  the  majority  of  them  are  morphologically 
indistinguishable  from  ordinary  acinous  cancer  (scirrhous). 

Of  170  women  with  mammary  cancer  consecutively  under  my 
observation,  in  no  less  than  31  (18-2  per  cent.)  the  disease  was  of  the 
chronic  type  ;  and  in  25  the  growth  was  morphologically  of  the  ordinary 
acinous  kind. 

The  disease  in  these  25  chronic  acinous  cancers  had  already  lasted  as 
follows  : — 5  to  10  years  in  14  cases  ;  10  to  15  years  in  6  cases  ;  15  to  20  years 
in  2  cases  ;  20  to  25  years  in  1  case  ;  and  over  25  years  in  1  case. 

Similarly,  of  64  consecutive  fatal  cases  that  had  run  their  natural 
course,  in  17,  or  26-5  per  cent.,  the  disease  had  lasted  for  upwards  of  five 
years  ;  and  of  these  14  were  of  the  ordinary  scirrhous  type. 

The  total  duration  of  life  in  these  14  chronic  scirrhous  cases,  was  as 
follows  : — 5  to  10  years  in  8  cases,  10  to  15  years  in  5  cases  ;  over  20  years 
in  1  case. 

I  have  seen  cases  in  which  the  disease  had  lasted  for  28,  24,  and  17 

1  "Cancer  of  the  Breast,"  1882,  p.  61. 

29 


450  THE  NATURAL  HISTORY  OF  CANCER 

years  respectively.  Nunn l  has  reported  an  instance  of  chronic  breast 
cancer,  in  which  the  total  duration  of  the  disease  had  exceeded  30  years  ; 
and  when  last  seen  the  patient  was  still  able  to  earn  her  living  as  a  char- 
woman. 

In  point  of  chronicity,  it  would  be  difficult  to  surpass  such  cases, 
even  among  the  atrophic  and  colloid  varieties  of  the  disease,  which  are 
generally  supposed  to  have  a  monopoly  in  this  respect. 

The  atrophic  form  of  cancer  is  certainly  rare,  for  of  170  consecutive 
mammary  cancers,  I  met  with  only  6  instances  of  it,  or  3-5  per  cent.  ; 
but,  according  to  Gross,  atrophic  varieties  constitute  7-9  per  cent,  of  all 
breast  cancers. 

The  characteristic  feature  of  this  type  is  the  continuous,  gradual 
shrinking  of  the  new  formation,  and  the  consequent  irregular  contraction 
of  the  breast,  which  is  often  thereby  diminished  rather  than  increased  in 
size.  The  deformity  produced  is  apt  to  resemble  that  met  with  in 
"  chronic  cirrhosing  mastitis."  These  atrophic,  cicatrizing  or  cirrhosing 
cancers,  usually  begin  with  obscure  hardness,  which  progresses  slowly, 
forming  at  length  ill-defined,  flattened  or  irregularly  nodulated  thickening, 
with  numerous  "  roots  "  stretching  far  into  the  adjacent  parts.  Such 
growths  consist  of  very  dense,  whitish,  dry,  fibroid  substance  ;  and,  on 
account  of  their  extreme  hardness,  they  have  not  inappropriately  been 
designated  "  stone  cancers." 

jjP  Histologically,  the  fibrous  stroma  preponderates,  while  epithelial 
elements  are  very  scanty,  or  altogether  wanting.  This  stroma  consists 
of  irregularly  disposed  bundles  of  fibrous  tissue,  rich  in  elastic  fibres,  but 
poor  in  cellular  elements.  It  contains  variously  shaped  small  spaces — 
atrophied  alveoli — in  which  are  a  few  degenerate  epithelial  cells,  or  merely 
cellular  debris  and  fatty  granules.  The  constituent  cells  of  cancers  of 
this  kind  are  very  short-lived,  for  no  sooner  have  they  formed  than 
they  thus  degenerate  ;  only  at  their  extreme  periphery,  are  proliferous 
epithelial  cells  to  be  found.  Usually  the  disease  runs  an  extremely 
chronic  course,  most  cases  lasting  for  from  ten  to  fifteen  years  or 
more. 

Atrophic  cancers  are  specially  prone  to  invade  extensively  the 
adjacent  tissues  by  direct  extension  ;  and,  in  a  less  degree,  by  local 
dissemination.  Lymph-glandular  and  general  dissemination,  although 
often  long  delayed,  are  seldom  absent ; 2  and  recurrence  after  operation 
is  of  frequent  occurrence.  The  secondary  growths  reproduce  the  atrophic 
characteristics  of  the  primary  one. 

In'  spite  of  the  chronicity  of  this  form  of  cancer,  it  never  seems  to 
undergo  spontaneous  cure. 

There  can  be  no  doubt  that,  under  the  term  colloid  cancer,  several 
different  varieties  of  chronic  malignant  disease  having  a  gelatiniform 
aspect,  are  commonly  included.  The  subject  requires  to  be  thoroughly 
reinvestigated,  in  the  light  of  modern  science.  Most  of  the  75  mammary 

1  Transactions  of  the  Clinical  Society,  London,  1872,  1878,  and  1896. 

For  a  case  of  twenty-three  years'  duration,  in  which  there  was  neither  lymph- 
glandular  nor  general  dissemination,  although  the  opposite  breast  and  adjacent  skin, 
etc.,  were  invaded,  vide  Bontor,  Transactions  of  the  Pathological  Society,  London,  1902. 


THE  MORPHOLOGY  OP  MALIGNANT  TUMOURS         451 

cases  collected  by  Lange 1  are  of  ancient  date,  imperfectly  recorded, 
defective  in  histological  details  and  in  other  respects. 

The  disease  is  certainly  rare,  since  of  170  consecutive  mammary 
cancers,  I  have  not  met  with  a  single  instance  of  it.  Lange  estimates 
that  only  0-93  per  cent,  of  all  breast  cancers  are  of  this  variety  ;  and  Gross' 
estimate  is  1-34  per  cent. 

Colloid  cancer  of  the  breast,  is  remarkable  for  the  slowness  of  its 
progress. 

The  disease  owes  its  peculiar  features  to  the  proneness  of  its  con- 
stituent cells  to  undergo  colloid  metamorphosis.  In  this  connexion  it 
must  be  remembered,  that  colloid  changes  normally  occur  in  the  secretory 
cells  of  the  gland,  during  the  early  stages  of  lactation. 

Sections  of  such  growths  reveal  small,  translucent  masses  of  glutinous 
fluid,  embedded  in  the  meshes  of  a  fibrous  stroma,  in  place  of  the  usual 
cellular  aggregations.  It  comparatively  seldom  happens,  however,  that 
the  whole  neoplasm  is  thus  affected  ;  for  some  parts  nearly  always  retain 
their  ordinary  scirrhous  character. 

Histological  examination  reveals  large,  thin-walled  alveoli,  distended 
with  colloid  fluid  containing  granular  debris,  in  which  only  a  few  degener- 
ated cells,  or  perhaps  none  at  all,  can  be  made  out.  Owing  to  these 
changes  in  the  cells,  their  growth  is  retarded,  and  the  malignancy  of  the 
disease  is  thereby  diminished  ;  hence  colloid  cancers  run  a  very  chronic 
course,  the  average  duration  of  life  being  about  twelve  years  ;  and  they 
are  more  tardily,  and  less  frequently,  followed  by  local,  lymph-glandular 
and  general  dissemination,  than  any  other  form  of  mammary  cancer. 
Moreover,  in  this  variety  of  the  disease,  cachectic  symptoms  seldom  super- 
vene. When  secondary  growths  do  arise,  in  their  main  features,  they 
resemble  the  primary  ones. 

Colloid  cancer  usually  begins  as  a  small,  lumpy  swelling  in  the  breast, 
which  increases  very  slowly.  The  resulting  tumour  seldom  exceeds  the 
size  of  a  hen's  egg,  and  it  may  take  from  ten  to  fifteen  years  to  attain  this 
size.  It  generally  feels  firm  and  elastic,  with  projecting  bosses.  As  these 
growths  do  not  shrink,  the  nipple  and  overlying  skin  are  much  less 
frequently  retracted  than  in  ordinary  scirrhus.  Ulceration  occasionally 
ensues  at  an  advanced  stage  of  the  disease.  Recurrences  are  less  frequent 
than  after  the  removal  of  any  other  form  of  mammary  cancer  ;  and,  when 
they  do  occur,  they  are  of  tardy  development,  rarely  supervening  until 
from  three  to  ten  years  after  operation. 

Many  cases  of  so-called  colloid  cancer  of  the  breast  are  really  examples 
of  carcinoma  myxomatodes.  In  this  variety  of  mammary  cancer,  the 
gelatinous  transformation  is  due  to  myxomatous  metaplasia  of  the 
fibrous  tissue  of  the  stroma  ;  and,  in  extreme  cases,  of  its  cellular  elements 
as  well.  Exceptionally,  it  may  even  happen  that  the  cancer  cells  them- 
selves thus  degenerate.  In  this  connexion  it  should  be  borne  in  mind, 
that  a  layer  of  mucoid  connective  tissue  is  normally  present,  immediately 
round  the  ducts  and  acini. 

A  sub-variety  occurs — to  which  the  term  cylindroma  has  been  applied — 
in  which  the  myxomatous  stroma  appears  as  if  more  or  less  enclosed  in 

1  Beitr.  z.  klin.  Chir.,  1896,  Bd.  xvi.,  S.  i. 

29—2 


452  THE  NATURAL  HISTORY  OF  CANCER 

the  epithelial  ingrowths  ;  but  only  a  few  examples  of  this  kind  have  been 
recorded. 

Uterus. According  to  my  calculation,  glandular  cancer  of  the  cervix 

uteri the  commonest  form  of  uterine  malignant  disease — runs  its  course 

from  beginning  to  end  in  about  two  years.1     Some  cases  progress  more 
rapidly  than  others  ;  but  chronic  varieties  are  comparatively  rare. 

Cases  that  run  their  entire  course  within  a  year,  I  reckon  as  of  the 
acute  variety.  Such  cases  are  by  no  means  rare  ;  for,  of  my  90  examples 
of  cervical  cancer,  24  were  acute,  or  26-6  per  cent.  ;  whereas,  only  15-6  per 
cent,  of  my  mammary  cancers  proved  fatal  within  this  brief  period. 
The  morphological  characteristics  of  such  growths,  are  usually  identical 
with  those  of  the  ordinary  cylinder- celled  glandular  cancer.  In  some 
exceptional  cases,  however,  the  morbid  epithelial  elements,  instead  of 
assuming  the  typical  tubular  form,  have  been  observed  to  be  irregularly 
diffused  in  the  surrounding  stroma,  as  in  certain  acute  cases  of  mammary 
cancer.  I  have  seen  it  stated,  that  uterine  cancers  of  this  kind  are  com- 
monest in  young  women,  recently  pregnant.  My  experience  gives  no 
support  to  this  statement.  In  not  a  single  one  of  my  acute  cases,  did 
the  disease  start  prior  to  the  age  of  30  ;  6  were  over  40,  2  over  50,  and  1  was 
68£  years  old  at  its  onset.  In  none  of  my  cases  did  the  debut  of  the  disease 
coincide  with,  or  occur  soon  after,  parturition. 

These  facts  indicate,  that  the  abnormally  rapid  progress  of  the 
neoplasm  depends  more  upon  the  intrinsic  properties  of  its  constituent 
cells,  than  upon  extraneous  influences.  The  most  rapidly  progressive 
case  of  my  list,  ran  its  entire  course  in  4-7  months.  Kiwisch  has  reported 
an  instance,  in  which  the  total  duration  was  only  five  weeks  ;  and  Martin's 
acutest  case  lasted  only  nine  weeks. 

Febrile  and  pseudo-inflammatory  complications  may  be  present ; 
and  widespread  generalization  of  the  disease  often  occurs. 

Chronic  cases,  that  is  to  say,  cases  in  which  the  total  duration  of  the 
disease  exceeds  three  years,  are  rarer  than  acute  ones.  Of  my  90  cervical 
cancers,  15  or  16-6  per  cent.,  were  of  this  kind.  In  3  cases  the  total  dura- 
tion of  life  exceeded  7  years.  My  most  chronic  case  lasted  over  7|  years, 
when  the  patient,  aged  52,  died  suddenly  from  the  bursting  of  a  pyo- 
nephrosis  into  the  peritoneal  cavity.  The  structural  characteristics  of 
these  chronic  growths  differed  in  no  respect,  from  those  of  the  ordinary 
cylinder-celled  glandular  cancers.  The  average  age  of  the  patients  was 
51  years ;  that  for  uterine  cancer  in  general  being  only  44  years. 
F.  Barker  has  reported  an  instance  of  uterine  cancer,  in  which  the  disease 
lasted  for  1 1  years. 

Cancer  of  the  corpus  progresses  less  rapidly  than  cancer  of  the  cervix, 
the  average  duration  of  life,  in  this  form  of  the  disease,  being — according 
to  Pichot — about  thirty-two  months. 

Odebrecht  has  described  a  case,  in  which  he  successfully  extirpated 
the  uterus  by  abdominal  section,  for  a  large  cancerous  tumour  of  the 
corpus,  that  was  known  to  have  existed  for  five  years  and  four 
months. 

Although  there  is  no  specific  difference  between  epidermoidal  and 
1  For  further  details,  vide  my  book  on  "  Uterine  Tumours,"  1901,  p.  195. 


THE  MORPHOLOGY  OF  MALIGNANT  TUMOURS         453 

other  forms  of  cancer  of  the  uterus  ;  yet,  this  form  of  the  disease  runs  a 
more  chronic  course,  than  is  usual  with  mucosal  cancer. 

The  tendency  of  these  epidermoidal  forms  is  to  spread  superficially 
rather  than  deeply ;  and  the  disease  progresses  towards  the  vagina, 
rather  than  towards  the  uterus.  At  a  later  stage,  the  pelvic  connective 
tissue  is  invaded,  as  well  as  the  bladder,  rectum  etc.  Eventually  dis- 
semination in  the  adjacent  pelvic  lymph-glands  may  occur,  but  metastases 
are  decidedly  rare. 

Certain  epidermoidal-celled  cancers  of  the  portio  occasionally  give 
rise  to  chronic,  shallow  forms  of  ulceration,  that  have  been  described  by 
such  names  as  "  corroding  ulcer,"  "  ulcus  rotundum  simplex,"  "  ulcus 
serpiginosum  "etc. 

Such  ulcers  have  slightly  raised,  sharply  cut,  sinuous  edges,  with  a 
comparatively  smooth  base,  irregularly  studded  with  small,  imperfectly 
formed  granulations,  which  in  places  have  a  florid  and  almost  healthy 
appearance.  A  thin,  parchment-like  layer  of  cancerous  growth  generally 
underlies  the  affected  area,  which  consists  of  solid  ingrowths  of  epi- 
dermoidal cells,  devoid  of  "  nests."  In  a  case  of  this  kind  that  I  investi- 
gated, the  disease  differed  in  no  essential  feature  from  "  rodent  ulcer." 

The  term  "  corroding  ulcer  "  was  first  applied  to  chronic  ulcerative 
disease  of  the  os  uteri  by  the  brothers  Clarke,  who  first  clearly  recognized 
the  condition.  They  thus  designated,  a  slowly  spreading,  superficial 
form  of  intractable  ulceration,  which  gradually  involved  the  whole  portio, 
and  eventually  destroyed  it.  The  duration  of  the  disease  was  often  ten 
years  or  upwards,  and  the  patients  affected  were  generally  over  forty  ; 
thus,  in  its  clinical  aspect,  it  precisely  resembles  rodent  ulcer  ;  but,  no 
anatomical  signs  of  cancer  are  usually  noticeable  in  connexion  with  it. 

Very  few  specimens  of  this  rare  affection  have  hitherto  been  submitted 
to  careful  histological  examination  ;  in  a  typical  example  recorded  by 
J.  Williams,  no  cancer  structures  were  detected. 

Too  much  importance  need  not  be  attached  to  a  few  negative  indica- 
tions of  this  kind,  since  the  epithelial  elements  in  rodent  ulcer  are  often 
scanty,  and  the  small  round-celled  infiltration  very  abundant ;  hence, 
long  after  Jacob  had  differentiated  rodent  ulcer  as  a  clinical  entity,  it 
was  nevertheless  classed  as  a  non-cancerous  disease.  Moreover,  instances 
of  tuberculous  ulceration  of  the  uterus,  especially  those  of  the  lupoid 
type,  have  no  doubt  often  been  described  as  "  corroding  ulcer."  As  to 
whether  any  form  of  ulcerative  disease,  answering  to  the  description  of 
"  corroding  ulcer,"  ever  occurs  in  the  uterus,  as  a  consequence  of  local 
malnutrition  dependent  upon  obliterative  arteritis  etc. — as  Beuttner, 
John  Williams  and  others  maintain — I  am  certainly  sceptical. 


CHAPTER    XX 
RECURRENCE 

No  feature  of  cancer  has  attracted  more  attention  than  that  which  is 
known  as  "  recurrence."  It  certainly  does  seem  extraordinary,  after 
everything  has  been  done  to  ensure  its  destruction— whether  by  the 
knife,  by  fire,  or  by  caustics — that  the  disease  should,  nevertheless,  so 
frequently  spring  up  again.  As  Lebert  says,  "  Recidive  est  la  regie  et 
'presque  la  loi" 

Before  attempting  to  explain  this  remarkable  phenomenon,  I  propose 
briefly  to  set  forth  the  chief  known  facts  relating  to  it. 

In  the  great  majority  of  these  cases,  the  recurrent  disease  makes  its 
first  appearance  in  the  locality  occupied  by  the  primary  disease,  less 
frequently  in  the  adjacent  lymph-glands,  and — rarest  of  all — in  remote 
parts  of  the  body. 

There  are  well-marked  differences  in  respect  to  recurrence  between 
sarcomatous  and  epitheliomatous  tumours ;  as  a  rule,  local  and  lymph- 
gland  recurrence  is  much  less  frequent  with  the  former  than  with  the 
latter  type  of  cancer,  while  as  to  metastatic  recurrence  it  is  just  the 
converse. 

Thus,  with  regard  to  malignant  epithelial  tumours  of  the  mamma, 
Gross'  analysis1  of  543  recurrences  shows  that  about  83  per  cent,  of  them 
were  located  in  the  mammary  region  (with  lymph-gland  recurrence  as 
well  in  23-5  per  cent.)  ;  and  in  the  axillary  glands  alone  in  15-5  per  cent. 

Of  47  recurrent  mammary  cancers  of  this  kind  under  my  observation, 
the  disease  first  reappeared  in  the  primarily  affected  mammary  region,  in 
21  cases  ;  in  the  mammary  region  and  in  the  axillary  glands,  at  about  the 
same  time,  in  18  cases  ;  and  in  the  axilla  alone,  in  8  cases. 

With  sarcomata  of  this  part  local  recurrence  is  much  rarer,  since  it 
was  met  with  only  in  21-4  per  cent,  of  my  cases,  in  25  per  cent,  of 
Schuoler's,  and  in  58  per  cent,  of  Gross'  ;  while,  with  this  form  of  the 
disease,  lymph-gland  recurrence  is  most  exceptional. 

In  1-61  per  cent,  of  Gross'  cases  of  epithelial  cancer  of  the  breast,  the 
disease  recurred  in  the  opposite  mamma  ;  in  2  of  14  cases  of  mammary 
adeno-sarcoma  under  my  observation,  there  was  recrudescence  of  the 
disease  in  the  opposite  breast,  but  none  at  the  primary  seat. 

Reappearance  of  the  disease  in  parts  of  the  body  not  directly  con- 
nected with  the  primary  epithelial  cancer  or  its  derivatives  (so-called 
metastatic  recurrence),  was  found  by  Gross  to  have  taken  place  in  178  out 

1  "American  System  of  Gynaxjology,"  vol.  ii.,  p.  301. 


RECURRENCE  455 

of  1,030  mammary  extirpations,  or  in  17  per  cent.  ;  but,  in  129  of  these 
cases,  there  was  local  or  lymph-gland  recurrence  as  well. 

With  regard  to  mammary  sarcoma,  there  is  no  information  available, 
showing  the  comparative  frequency  of  metastatic  recurrence. 

Local  recurrences,  when  first  noticed,  usually  present  as  small  nodules  ; 
their  initial  situation  being  either  in  the  operation  scar,  or  its  immediate 
vicinity — rarely  elsewhere.  There  has  been  much  discussion,  as  to 
whether  these  recurrent  lesions  are  of  more  frequent  occurrence  in  the 
cicatrix  of  the  operation  wound,  or  in  its  vicinity.  It  is  now  generally^ 
agreed,  that  the  latter  is  the  seat  of  their  maximum  incidence  ;  thus,  of 
Halstead's :  mammary-cancer  extirpations,  16  per  cent,  recurred  in  the 
structures  adjacent  to  the  operation  scar,  as  against  6  per  cent,  in  the 
scar. 

Considering  the  frequency  with  which  radical  operations  are  now 
being  done  for  uterine  cancer,  it  is  regrettable  that  the  phenomena  of  its 
recurrence,  have  not  yet  been  studied  with  that  thoroughness  which  is 
desirable. 

It  has,  however,  been  clearly  ascertained  ;  that,  in  the  immense 
majority  of  cases,  the  recurrent  lesions,  which  are  almost  invariably 
multiple,  make  their  first  appearance  in  the  locality  of  the  primary  disease, 
or  in  the  region  immediately  adjacent  thereto. 

Most  observers  are  agreed  that — after  partial  hysterectomy — it  is  in 
the  para-cervical  and  para- vaginal  tissues,  adjacent  to  the  extirpated 
part,  rather  than  in  the  uterine  stump,  that  recurrent  lesions  first  appear  ; 
and,  after  more  radical  operations,  it  is  in  the  adjacent  para-metrium 
that  the  disease  first  reappears. 

Thus,  of  58  recurrences,  after  the  extirpation  of  cervical  cancer, 
Winter2  found  that  54  were  in  this  locality  ;  and  Hofmeier3  reports  that 
of  47  operated  cases — in  which  recurrence  took  place  during  the  first  year 
after  partial  vaginal  hysterectomy — the  disease  reappeared  in  the  ad- 
jacent para-metrium  in  45  cases. 

It  appears  to  be  rare  for  the  initial  manifestation  of  recurrence,  to 
originate  in  the  ilio-pelvic  or  lumbar  glands  ;  but  I  know  of  no  really 
satisfactory  observations  bearing  directly  on  this  subject.  Winter, 
however,  states  that  he  has  never  observed  a  case  of  this  kind  ;  and  of 
44  necropsies — after  total  extirpation  of  the  cancerous  uterus — lymph- 
gland  recurrence  was  found  only  in  2  cases. 

As  to  the  relative  frequency  of  recurrence  in  the  ovaries,  tubes,  and 
adjacent  parts  of  the  broad  ligaments — when  these  have  been  left  behind 
— there  is  also  lack  of  precise  information. 

So-called  metastatic  recurrences  are  extremely  rare  ;  for,  Winter  met 
with  only  9  instances,  after  202  operations. 

If  we  compare  with  these  epithelial  cancers,  the  recurrences  of  sar- 
comata of  the  choroid  and  femur,  marked  differences  are  noticeable. 

Thus  of  285  intra-ocular  sarcomata,  for  which  the  diseased  eye  had 
been  removed,  Fuchs4  found  local  recurrence  in  only  31,  or  in  13  per  cent.  ; 

1  Johns  Hopkins  Hospital  Report,  1894,  vol.  iv.,  No.  6. 

2  Zeits.  f.  Geb.  u.  Oyn.,  Bd.  xxvii.,  S.  101  ;  also  ibid..  1892,  Bd.  xxiv.,  S.  141. 

3  Ibid.,  Bd.  xxxii.,  S.  97.  *  "  Das  Sarcoma  des  Uvealtractus,"  Wien,  1882. 


456 


THE  NATURAL  HISTORY  OF  CANCER 


and  lymph-gland  recurrence  was  hardly  ever  noted  ;  but,  of  those  who 
died  after  the  operation,  nearly  all  succumbed  to  metastatic  recurrence.  . 

Similarly,  of  103  cases  tabulated  by  Lawford  and  Collins,1  local 
recurrence  was  noted  in  only  7  instances,  and  lymph-gland  recurrence  not 
at  all ;  but,  23-9  per  cent,  of  those  who  had  survived  extirpation  of  the 
eye,  were  known  to  have  died  of  metastatic  recurrence. 

Of  14  recurrences,  after  amputation  for  periosteal  sarcoma  of  the 
femur,  tabulated  by  Butlin,2  7  were  local,  and  7  metastatic. 

The  period  at  which  recurrences  first  present  is  exceedingly  variable  ; 
and  the  numerical  results  obtained  by  different  investigators  are  often 
divergent. 

Of  47  consecutive  mammary  epithelial  cancer  cases,  under  my  obser- 
vation, the  average  interval  between  the  operation  and  the  first  obvious 
recurrence  was  26  months,  the  maximum  130  months,  the  minimum  a 
few  weeks.  These  results  are  more  favourable  than  those  arrived  at  by 
my  predecessors  ;  thus,  according  to  Gross,  the  average  period  of  immunity 
only  amounts  to  9-4  months. 

The  elaborate  analysis  by  Rieffel,3  of  687  operated  mammary-cancer 
cases,  shows  the  periods  at  which  recurrences  may  be  expected,  as  follows  : 


Interval  between  Operation  and  First  Obvious  Recurrence. 

Total 
Number 
of  Cases. 

Per- 
centage 
Numbers. 

First  to  end  of  fourteenth  day 

35 

5'09 

Fifteenth  day  to  end  of  first  month 
Second  month  to  end  of  third  month 

91 
181 

13-24 
26-34 

Fourth  month  to  end  of  sixth  month 

137 

19-94 

Seventh  month  to  end  of  ninth  month 

75 

10-91 

Tenth  month  to  end  of  twelfth  month 

52 

7-28 

Thirteenth  month  to  end  of  eighteenth  month 
Nineteenth  month  to  end  of  twenty-fourth  month 

54 
17 

7-83 
2-47 

Second  year  to  two  and  a  half  years 
Two  and  a  half  years  to  three  years 

11 

10 

T60 
1'45 

Three  years  to  four  years 

15 

2-18 

Over  four  years 

9 

1-31 

Totals 

687 

99-64 

From  this  table  it  will  be  gathered,  that  about  64  per  cent,  of  all 

<x  mammary-cancer  recurrences  take  place  within  the  first  six  months  after 

operation  ;  and,  of  these,  about  44  per  cent,  originate  within  the  first 

three  months.     Over   18  per  cent,  occur  within  the  first  month,   and 

5  per  cent,  within  the  first  fifteen  days.     The  proportion  of  recurrences 

attributed  by  Gross  and  Winiwarter  to  the  first  month,  is  considerably 

higher  than  the  above-mentioned  figure.      Less  than  4  per  cent,  of  all 

recurrences  originate  after  the  third  year  ;  and,  after  the  fourth  year, 

>  the  number  is  much  smaller.      On  the  other  hand,  over  82  per  cent. 

of  all  recurrences  originate  during  the  first  year  after  operation. 


1  Royal  London  Ophthalmic  Hospital  Reports,  December,  1891, 
1  "  Operative  Surgery  of  Malignant  Disease,"  1887,  p.  49. 


vol.  xli. 


3  "  De  quelques  points  relatifs  aux  recidives  et  aux  generalisations  des  cancers  du 
sein  chez  la  femme  "  (These  de  Paris,  1890). 


RECURRENCE 


457 


The  following  tabular  statement,  based  on  144  cases  of  cancer  of  the 
cervix  uteri  collected  by  Hache,  shows  the  periods  at  which  recurrence 
may  be  expected  after  complete  vaginal  hysterectomy. 


Under  3  months 
3  to  6  months 
6  to  9  months  
9  to  12  months  
12  to  18  months 
18  to  24  months 
2  to  3  years 

.  i 

n  19'4  per 
18'0 
10'5 
7'6 
12'5 
9'8 
14'6 
7'6 

cent. 

Over  3  years        

From  this  we  learn  that  over  55  per  cent,  of  all  recurrences  belong  to 
the  first  year  ;  and  that,  nearly  20  per  cent,  of  these  originate,  during  the 
first  three  months.  On  the  other  hand,  only  7-6  per  cent,  of  recurrences 
appear  after  the  third  year. 

The  incidence  of  recurrence  is  much  influenced  by  the  stage  of  the 
disease  at  which  operative  interference  is  undertaken  ;  as  well  as  by  the 
more  or  less  thorough  nature  of  the  operative  procedure  adopted  ;  and 
probably,  to  some  extent,  by  the  seat  of  the  primary  disease. 

Thus  the  liability  to  local  recurrence,  after  the  extirpation  of  mammary 
cancer,  has  been  reduced  by  the  earlier  and  more  thorough  operative 
procedures  now  in  vogue,  from  over  82  per  cent.,  to  50  per  cent.,  and 
even  less  ;  while,  at  the  same  time,  the  proportion  of  patients  well  and  free 
from  any  return  of  the  disease,  for  upwards  of  three  years  afterwards, 
has  increased  from  less  than  4  per  cent.,  to  from  20  to  30  per  cent.' 

Similarly,  Leopold  found  that  of  59  early  operated  cancers  of  the 
cervix  uteri — in  which  there  were  no  signs  of  extension  of  the  disease  to 
the  para-metrium — recurrence  took  place  in  14,  or  in  23-7  per  cent. ; 
whereas,  of  68  advanced  cases — in  which  the  para-metrium  was  obviously 
involved — there  was  recurrence  in  45,  or  in  66-1  per  cent.  Krukenberg's 
data  are  of  similar  import.  Ott  reports  that  of  8  early  vaginal  total 
hysterectomies,  7  patients  were  still  free  from  any  return  of  the 
disease,  for  periods  varying  from  one  to  over  three  years  after  operation, 
and  in  only  1  patient  had  the  disease  recurred  within  one  year  after 
extirpation  ;  whereas,  after  9  similar  late  operations,  recurrence  followed 
in  every  case,  at  periods  varying  from  one  to  eleven  months.  These 
figures  show  the  necessity  for  early  operation. 

Another  effect  of  thorough  operations  has  been,  to  add  considerably 
to  the  duration  of  the  life  of  those  who  have  survived  them. 

I  have  tabulated  all  the  fatal  cases  of  breast  cancer,  that  came  under 
my  observation  at  the  Middlesex  Hospital,  during  a  period  of  six  years, 
with  the  result  that  the  average  duration  of  life — dating  from  the  time 
when  the  disease  was  first  noticed — was  60-8  months  for  those  who  under- 
went operation,  and  44-8  months  for  those  in  whom  the  disease  ran  its 
natural  course.  Thus,  the  average  duration  of  life  for  the  operated  cases, 
was  16  months  longer  than  for  the  non- operated  ;  and,  after  extirpation  of 
the  primary  disease,  the  former  lived — on  the  average — for  40-3  months, 
that  is  to  say,  nearly  as  long  as  the  entire  duration  of  the  life  of  the  non- 
operated.  Moreover,  the  number  of  those  who  died  before  the  end  of 
the  third  year  after  operation  was  40  per  cent.  ;  whereas,  of  the  non- 


458  THE  NATURAL  HISTORY  OF  CANCER 

operated,  the  number  who  died  prior  to  this  period  was  53  per  cent. 
In  cancer  of  other  localities,  equally  good  results  have  followed  bold 
attempts  to  completely  extirpate  the  disease. 

Second  recurrences  are  fairly  common.  I  have  met  with  them  in  8 
out  of  43  recurrent  mammary  cases  (18-6  per  cent.)  ;  and  Rieffel,  in  134 
out  of  687  such  cases  (19-5  per  cent.).  The  earliest  date  at  which  second 
recurrences  appeared,  in  the  8  cases  under  my  observation,  was  a  few  days 
after  the  operation  ;  the  latest,  130  months  after ;  and,  the  average 
interval,  was  23-2  months.  In  these  same  8  cases,  the  first  recurrence 
appeared  on  the  average  41-5  months  after  operation.  This  supports 
Thiersch's  dictum,  that  the  interval  between  operation  and  recurrence, 
tends  to  shorten  with  each  successive  operation. 

Third  recurrences  are  rare  :  there  was  only  1  instance  of  the  kind 
among  the  43  recurrent  mammary  cancers  of  my  list  (2-3  per  cent.), 
and  30  among  Rieffel's  687  cases  (4-3  per  cent.). 

Fourth  recurrences  are  so  highly  exceptional,  that  Rieffel's  list  of  687 
recurrent  cases  comprises  only  7  instances,  or  rather  more  than  1  per  cent. 

Many  instances  of  patients  remaining  free  from  return  of  the  disease, 
after  two  or  more  operations  for  recurrence,  have  been  reported  ;  Plicque 
has  collected  the  records  of  97  cases  of  this  kind.  Poulsen  has  also 
reported  instances  in  which,  during  the  first  year  or  two  after  the  initial 
operation,  one  or  more  recurrent  tumours  had  been  removed  ;  yet,  the 
patients  were  well  and  free  from  any  return  of  the  disease,  from  eight  to 
nine  years  after  the  last  operation.  Gouley  x  has  met  with  2  cases  of 
recurrent  breast  cancer,  under  observation  twenty  and  twenty-five  years 
respectively  after  the  first  operation,  in  which  the  patients  were  well  and 
free  from  recurrence  when  last  seen — upwards  to  five  years  after  the  last 
operation. 

I  shall  subsequently  have  to  refer  to  other  instances  of  this  kind. 
After  excision  of  epithelioma  of  the  lower  lip,  recurrent  for  the  third 
time,  J.  Hutchinson  2  had  the  satisfaction  to  find  his  patient  free  from 
any  return  of  the  disease,  fifteen  years  later. 

It  is  in  the  operative  treatment  of  the  less  malignant  forms  of  sarcoma, 
that  recurrences  are  most  frequently  encountered.  In  dealing  with 
mammary  sarcomata  of  this  kind,  as  many  as  4,  5,  6,  7,  12  operations  and 
upwards  for  recurrent  disease,  have  often  been  reported. 

In  a  remarkable  case  of  small  spindle-celled  sarcoma  of  the  breast, 
in  a  single  woman  aged  forty-four,  as  described  by  Gross,3  22  operations 
were  done  and  54  recurrent  tumours  removed,  in  the  short  space  of  four 
years.  Yet,  when  last  heard  of,  over  ten  years  after  the  final  operation, 
this  patient  was  in  good  health  and  free  from  any  return  of  the  disease. 

Occasionally  recurrence  sets  in  immediately  after  operation,  as  in  the 
following  case  under  my  observation  : — 

A  stout,  healthy-looking  woman,  aged  sixty-eight,  with  very  large 
mammae,  had  a  movable  tumour — of  three  months'  growth  and  the  size 
of  a  turnip — in  the  middle  of  her  right  breast.  There  was  no  obvious 

1  New  York  MedicalJournal,  1888,  vol.  ii.,  p.  396. 

2  Archives  of  Surgery,  April,  1892,  p.  339. 

3  "  American  System  of  Gynaecology,"  vol.  ii.,  p.  247. 


RECURRENCE  459 

implication  of  the  axillary  lymph-glands.  The  breast  was  amputated, 
without  opening  the  axilla.  Immediately  afterwards,  acute  diffuse  re- 
currence set  in,  which  involved  the  whole  wound.  The  skin,  pectoral 
and  intercostal  muscles,  ribs  and  pleura,  were  quickly  infiltrated.  Six 
weeks  after  operation,  death  ensued  from  hydrothorax  and  collapse  of 
the  right  lung,  owing  to  direct  extension  of  the  disease  through  the  chest 
wall.  At  the  necropsy,  the  right  parietal  pleura  was  found  to  be  studded 
throughout  with  cancerous  nodules  ;  and  it  showed  signs  of  recent  acute 
inflammation.  The  diaphragm  and  liver  contained  numerous  secondary 
growths,  but  none  were  present  in  either  of  the  lungs,  nor  in  the  left  pleura. 
It  was  a  case  of  acute  traumatic  malignancy,  after  operation. 

At  other  times,  recurrence  is  delayed  for  many  years — even  for  from 
twenty  to  thirty  years  ;  thus,  of  250  mammary-cancer  patients  operated 
on  by  Velpeau,1  20  remained  free  from  recurrence  for  periods  of  from 
five  to  twenty-seven  years,  or  1  in  12|.  Nunn  2  and  others  have  had 
similar  results.  Of  the  47  recurrent  mammary  cases  in  my  list,  there  are, 
however,  only  2  instances,  in  which  the  period  of  immunity  extended  to 
ten  years. 

A  striking  example  of  tardy  recurrence  is  afforded  by  members  of  the 
family,  whose  history  Sibley3  has  recorded,  in  which  the  mother  and  her 
five  daughters  all  had  cancer  of  the  left  breast.  Two  of  these  sisters 
passed  eleven  and  twelve  years  respectively,  after  removal  of  the  primary 
disease,  without  recurrence  ;  and,  upon  its  return  at  those  dates  and 
repetition  of  the  operation,  each  remained  free  from  its  return  for  seven 
years  more,  and  they  were  still  free  when  last  heard  of. 

The  two  following  cases  of  late  recurrence  have  come  under  my  own 
observation  : — 

Case  1. — An  emaciated  woman,  aged  sixty-two,  with  a  large,  hard 
mass  of  ulcerated  recurrent  cancer  in  the  right  mammary  region,  and 
cancerous  glands  in  the  axilla  and  lower  part  of  the  neck.  About  twelve 
years  previously  she  first  noticed  a  lump  in  her  right  breast,  which  was  am- 
putated soon  afterwards.  Ten  years  afterwards,  several  small  recurrent 
nodules  appeared  in  the  vicinity  of  the  scar  and  in  the  axilla  ;  which  were 
soon  afterwards  excised.  Six  months  later  the  present  recurrence  set  in. 
No  further  operation  was  done.  She  died  of  pulmonary  complications, 
apparently  due  to  invasion  of  the  chest  by  the  local  disease,  some  two 
and  a  half  months  later. 

Case  2. — A  well-nourished,  healthy-looking  woman,  aged  fifty-eight, 
with  a  nodule  of  atrophic  recurrent  cancer — the  size  of  a  hazel-nut — at 
about  the  middle  of  the  old  scar  in  the  left  mammary  region  ;  and  no 
obvious  enlargement  of  the  axillary  glands.  Twenty  years  previously  she 
first  noticed  a  small,  hard  lump,  in  the  middle  of  her  left  breast.  It  slowly 
increased.  Ten  years  later  the  breast  was  amputated.  She  remained 
quite  free  from  any  return  of  the  disease  until  six  months  ago,  when  the 
present  recurrence  was  first  noticed.  It  was  excised,  and  the  wound  had 
healed  a  fortnight  later. 

1  "Traite  des  Maladies  du  Sein,"  Paris,  1854. 

2  "  Cancer  of  the  Breast,"  1882,  p.  45. 

3  Medico-Chirurgical  Society's  Transactions,  vol.  xlii.,  p.  111. 


460  THE  NATURAL  HISTORY  OF  CANCER 

The  longest  period  of  immunity  known  to  me,  is  in  cases  reported  by 
Heurtaux  *  and  Verneuil,2  in  each  of  which  the  disease  recurred  in  situ, 
thirty  years  after  extirpation  of  the  breast  for  the  primary  cancer. 
Bryant  3  has  seen  similar  recurrence,  in  the  same  local  form  of  the  malady, 
after  twenty-five  years  immunity  ;  and  Nunn  4  after  sixteen  years. 

Pean  5  has  seen  local  recurrence  set  in,  twenty-five  years  after  ampu- 
tation of  the  breast,  for  primary  adeno-cystic  sarcoma. 

Bucher6  reports  recrudescence  of  cancer  in  the  opposite  breast,  six 
years  after  extirpation  of  its  fellow  for  the  primary  disease,  without 
recurrence  in  situ. 

I  have  previously  referred  to  Schmidt's  case,7  in  which,  seven  years 
after  extirpation  of  the  breast  for  primary  cancer,  without  local  recur- 
rence, there  was  return  of  the  disease  in  the  liver  and  lungs. 

Such  cases  illustrate  the  extraordinary  differences  that  obtain  in 
relative  malignancy,  between  cancers  of  the  same  variety — morpho- 
logically indistinguishable — in  the  same  locality,  and  apparently  under 
similar  conditions. 

With  cancer  of  the  cervix  uteri,  very  late  recurrences  are  of  much 
more  exceptional  occurrence,  than  very  early  ones. 

Pamard  8  has  reported  a  case  of  the  recurrence  of  cervical  cancer, 
fifteen  years  after  the  extirpation  of  the  primary  disease  by  supra- vaginal 
amputation,  with  the  galvano-caustic  wire-snare.  The  diagnosis  was 
histologically  verified. 

Fraenkel 9  has  seen  recurrence,  eight  years  after  removal  of  the 
primary  disease,  which  was  squamous  epithelial  cancer  of  the  portio. 

It  is  most  exceptional  for  recurrence  to  supervene,  after  total  hyster- 
ectomy, at  a  later  period  than  4  years  subsequently  to  the  operation  ; 
but,  Leopold  reports  having  met  with  recurrence  first  appearing  at  8,  7, 
6£,  and  5f  years  respectively,  after  hysterectomy. 

In  cancer  of  other  parts  of  the  body,  similar  instances  of  tardy  re- 
currence may  also  be  met  with. 

Guinard  10  has  seen  lingual  cancer  recur,  in  the  adjacent  part  of  the 
right  half  of  the  tongue,  18£  years  after  extirpation  of  the  left  half,  for 
primary  epithelioma,  without  any  return  of  the  disease  in  the  interval  ; 
and  of  Kocher's  u  reported  "  cures,"  after  extirpation  of  the  tongue  for  the 
primary  disease,  in  two  the  malady  is  known  to  have  returned  in  situ, 
10  and  12  years  respectively  afterwards  ;  and,  in  one  other  "  cured  " 
case,  the  patient  died  7  years  after  extirpation,  of  cancer  of  the  stomach. 

In  2  of  15  cases  of  recurrent  cancer  of  the  lower  lip  under  my  observa- 
tion, there  was  recrudescence  of  the  disease  6|  and  8£  years  respectively, 
after  the  primary  extirpation  :  in  the  former  of  these  cases,  the  operation 
scar  at  the  middle  of  the  lip  was  quite  healthy-looking,  the  recurrent  cancer 
being  distinct  from  it— at  the  outer  part  of  the  left  half  of  the  lower  lip  ; 

Arch.  Prov.  de  Chir.,  1899,  No.  2.  2  La  Semaine  Med.,  1888,  p.  112. 

"  Diseases  of  the  Breast,"  1887,  p.  158.  *  Op  cit 

Lemons  de  Clin.  Chir.,  1892,  p.  960. 

Ziegler's  Beitr.  z.  path.  Anat.,  etc.,  1893,  Bd.  xiv.,  S.  94. 

Beitr.  z.  klin.  Chir.,  Bd.  iv.,  Heft  1.  8  La  Gynecologic,  February  15,  1899. 

Cent.  f.  Gyn.,  1890,  Bd.  xiv.,  S.  891. 

Bull,  et  Mem.  de  la  Soc.  de  Chir.  de  Paris,  1903,  No.  14. 

"  Text-book  of  Operative  Surgery,"  1895. 


RECURRENCE  461 

in  the  latter  of  these  cases,  the  operation  scar  was  also  quite  sound,  the 
disease  having  reappeared  in  the  glands  of  the  neck. 

Thirteen  and  a  half  years  after  extirpation  of  buccal  epithelioma, 
Haberer  J  found  recurrence  in  situ,  the  patient  having  remained  well  and 
free  from  return  of  the  disease,  in  the  interval. 

An  interesting  case  has  been  recorded  by  Fisher  and  Box  2  of  a  man, 
whose  eye  having  been  extirpated  for  a  malignant,  pigmented,  intra- 
ocular tumour  of  the  ciliary  region,  14  years  later  died  of  a  large,  pig- 
mented, malignant  tumour  of  the  liver,  similar  in  structure  to  the  primary 
intra-ocular  tumour,  of  which  there  had  been  no  local  return. 

In  the  preceding  chapter  I  instanced  a  similar  case  by  Hulke,  in  which 
the  period  of  immunity  was  over  10  years. 

English  3  has  also  reported  an  instance  of  death  from  recurrence  in 
the  liver,  21  £  years  after  extirpation  of  the  primary  disease — cancer  of 
the  rectum — without  any  other  recrudescence  of  the  malady. 

These  examples  of  tardy  recrudescence  of  the  disease  show,  that  it  is 
impossible  to  fix  on  any  arbitrary  time  limit,  beyond  which  there  is  no 
risk  of  recurrence. 

As  mentioned  in  the  opening  chapter  of  this  work,  recurrence  per  se 
cannot  be  regarded  as  pathognomonic  of  malignancy.  It  accords  with 
this,  that  some  of  the  most  inveterate  and  striking  instances  of  recurrence 
are  met  with  among  tumours,  not  otherwise  remarkable  for  their  malig- 
nancy, such  as  rodent  ulcer,  spindle-celled  and  myeloid  sarcoma,  keloid 
etc.  Moreover,  non-malignant  tumours  sometimes  form  again  after 
removal,  in  the  same  locality  ;  and  occasionally  these  recurrent  tumours 
manifest  malignant  properties,  notwithstanding  the  benignancy  of  the 
primary  tumour,  of  which  many  instances  have  been  met  with  after  the 
removal  of  non- malignant  ovarian  cystoma  etc. 

Some  non-malignant  tumours,  such  as  subungual  exostosis  of  the 
great  toe,4  condylomata,  warts  etc.,  commonly  recur  after  removal,  unless 
the  tumour  matrix  is  thoroughly  extirpated. 

Even  with  such  affections  as  macrodactyly,  the  giant  growth  has  been 
known  to  recur  in  the  previously  normal  stump,  after  amputation  of  the 
affected  part  together  with  its  phalanges,  of  which  Settegart 6  has  reported 
an  interesting  example  ;  and  Sato  6  has  seen  recurrence,  after  the  extir- 
pation of  a  redundant  mammary  structure. 


Recurrence  of  Ovarian  Cystoma. 

Here  it  seems  desirable  briefly  to  consider  the  chief  facts  as  to  recur- 
rence, after  the  removal  of  non-malignant  tumours,  especially  ovarian 
cystoma,  as  such  knowledge  throws  light  on  some  of  the  obscure  problems 
relating  to  the  recurrence  of  malignant  tumours  ;  and,  the  time  has 

1  Wien.  klin.  Woch.,  1902,  No.  35. 

2  British  Medical  Journal,  1900,  vol.  i..  p.  639. 

3  Lancet,  1904,  vol.  ii.,  p.  596. 

*  Vide  an  essay  by  the  author  on  "  Subungual  Exostosis,"  Bristol  Medico-Chirurgical 
Journal,  March,  1904,  p.  17. 

5  Berlin,  klin.  Woch.,  November  9,  1906,  S.  1007. 

6  Lancet,  1907,  vol.  ii.,  p.  753. 


462  THE  NATURAL  HISTORY  OF  CANCER 

come,  when  it  ought  to  be  rescued  [from  the  obscurity  of  the  dispersive 
specialities. 

After  the  removal  of  one  or  both  ovaries  by  laparotomy  for  non- 
malignant  cystoma,  recurrence  occasionally  ensues  in  the  form  of  cystic 
disease  like  the  original ;  but  sometimes,  under  similar  circumstances,  a 
cancerous  form  of  recurrence  supervenes. 

Ovariotomy  statistics  show  that  non-malignant  recurrences  are  met 
with,  in  from  2-5  to  3-5  per  cent,  of  all  operations  for  benign  cystoma. 
The  usual  seat  of  these  secondary  tumours  is,  in  the  vicinity  of  the 
original  cystoma  ;  but,  they  may  be  found  in  any  part  of  the  track  of  the 
operation  wound.  Such  tumours  generally  arise  from  remnants  of  the 
original  tumour  left  behind  at  the  primary  operation,  or  from  fragments 
detached  and  implanted  in  the  wound  or  its  vicinity  ;  and,  in  the  event 
of  antecedent  rupture  of  the  cystoma,  detached  secondary  tumours  may 
be  found  at  the  time  of  the  initial  operation. 

After  the  removal  of  a  unilateral  cystoma  without  interference  with 

the  opposite  sound  ovary,  fresh  cystic  disease  may  develop  in  the  latter, 

as  many  reported  cases  testify.      Cystic  disease  of  a  sound  ovary,  left 

'  behind  after  removal  of  the  myomatous  uterus  together  with  a  diseased 

ovary,  has  also  been  noted,  as  in  a  case  lately  reported  by  Calmann. 

Even  bits  of  normal  ovarian  tissue,  such  as  are  sometimes  left  behind 
after  oophorectomy,  may  subsequently  originate  cystic  tumours,  of 
which  examples  have  been  recorded  by  Martin,  Pozzi,  P.  Miiller  and  others. 

Here  it  may  be  remarked,  that  recurrent  tumours  of  the  kind  we  are 
now  considering,  have  been  known  to  form  even  after  the  most  radical 
operations,  involving  extirpation  en  masse  of  the  ovaries,  uterus  and 
adnexa  ;  when  it  is  highly  improbable  that  any  fragments  of  the  ovaries — 
normal  or  cystic — could  possibly  have  been  left  behind. 

Even  if  the  presence  of  aberrant  accessory  ovarian  structures  in  the 
pelvic  region  and  its  vicinity,  had  never  been  actually  demonstrated,  I 
maintain  that  it  would  nevertheless  be  possible,  for  one  thoroughly 
acquainted  with  the  ensemble  of  the  facts  relating  to  conditions  of  this 
kind,  to  predicate  that  such  aberrant  structures  do  exist.  But  accessory, 
detached,  ovarian  structures  have  many  times  been  detected,  not  only  in 
the  immediate  vicinity  of  the  ovary  ;  but  also  in  the  broad  ligaments, 
and  in  more  remote  localities — intra-  and  extra-peritoneal.  To  this 
source  may  be  ascribed  many  of  the  recorded  cases  of  ovarian-like  cysto- 
mata,  arising  primarily  in  para-Uterine,  para-vaginal  and  para-vesical 
regions,  in  the  round  ligaments,  and  even  in  the  lower  part  of  the 
abdomen,  quite  outside  the  peritoneum  (Fergusson,  Meredith,  Olshausen, 
Kaltenbach,  Winternitz,  and  others).  Moreover,  dermoid  and  Wolffian 
structures  have  been  found  associated  with  these  tumours,  as  with  their 
ovarian  congeners. 

It  quite  accords  with  this  explanation,  that  menstruation  is  fairly 
often  re-established  after  double  oophorectomy  for  various  morbid  con- 
ditions  of  non-ovarian  origin,  as  well  as  after  double  ovariotomy  for 
cystoma  ;  and  pregnancy  has  often  been  known  to  ensue,  after  both  of 
these  types  of  operation. 

It  is  to  aberrant  accessory  ovarian  structures  of  this  kind,  that  we 


RECURRENCE  463 

must  look  for  the  origin  of  many  of  these  recurrent  ovarian  cysto- 
mata. 

Velitz  x  has  collected  and  analysed  135  cases  of  recurrent  ovarian 
cystoma  ;  in  56  of  these,  the  second  operation  was  for  the  removal  of 
cystic  disease  which  had  supervened  in  the  ovary  left  behind  at  the  first 
operation  ;  and,  in  14  other  cases,  for  recurrent  disease  otherwise  arising. 
In  8  cases,  a  third  operation  was  necessary  ;  and  in  1,  five  operations  were 
required. 

The  period  at  which  these  benign  recrudescences  of  cystoma  first  attract 
notice,  varies  from  1  year  to  over  20  years,  after  the  initial  operation  ; 
but,  a  relatively  large  proportion  of  them  are  of  tardy  development, 
that  is  to  say,  they  are  not  noticed  until  from  5  to  10  years  or  more 
after  operation. 

It  follows  from  what  has  been  stated,  that  the  germs  of  these  recurrent 
cystomata  are  either  detached  fragments  of  the  original  tumour  ;  or 
ovarian  tissue,  left  behind  at  the  initial  operation — in  the  form  either  of 
an  unextirpated  entire  ovary,  of  detached  fragments  of  a  normal  ovary, 
or  of  accessory  ovarian  structures,  subsisting  in  the  vicinity  of  the 
ovary,  or  at  some  distance  from  it. 

In  this  connexion  we  must  also  bear  in  mind,  that  polycystic  quasi- 
ovarian  tumours  may  possibly  arise  from  adrenal  "  rests  "  in  the  vicinity 
of  the  ovary,  according  to  Pick  and  Eastwood  ;  although,  it  seems  to  me, 
that  the  adrenal  origin  of  neither  of  their  tumours  has  been  clearly  proved. 

In  very  exceptional  instances,  similar  forms  of  local  recrudescence 
are  met  with,  after  the  removal  of  uterine  myoma,2  mammary  fibro- 
adenoma ;  and  other  non-malignant  tumours. 

We  are  now  in  a  position  to  examine  the  numerous  cases  recorded  of 
late,  in  which  the  removal  of  a  non-malignant  ovarian  cystoma  has  been 
followed  by  the  outbreak  of  cancer. 

These  cases  may  be  divided  into  three  categories. 

In  the  first  may  be  placed  those  rather  numerous  instances,  in  which 
it  seems  obvious  that  the  cancerous  disease  has  originated  from  detached 
fragments  of  the  original  cystoma,  implanted  in  the  track  of  the  operation 
wound  or  its  vicinity,  or  left  behind  in  situ.  Growths  of  this  kind  have 
been  met  with  in  the  cicatrix  of  the  abdominal  wall ;  in  the  site  of  the 
removed  cystoma,  its  pedicle,  or  adjacent  structures ;  and  diffused 
throughout  the  peritoneal  cavity.  Most  cases  of  this  kind,  develop 
within  a  few  years  after  the  original  operation.  In  these  cases^  it  seems 
as  if  proliferous  cells  detached  from  the  non-malignant  cystoma,  subse- 
quently acquired  malignant  properties,  owing  to  their  altered  conditions 
of  existence. 

In  the  second  class,  are  those  cases  in  which,  after  the  removal  of 
non-malignant  unilateral  cystoma,  cancer  supervenes  in  the  sound  ovary, 
of  which  I  know  of  several  instances  ;  in  like  manner,  as  many  cases 
indicate,  cancer  may  arise  from  accessory  ovarian  structures,  left  behind 
at  the  first  operation. 

1  Zcitschr.  f.  Geb.  u.  Oyn.,  Bd.  xx.,  Heft  2. 

2  Recent  cases  by  Diirch  (Munch,  med.    Woch.,  1907,  No.  22,  S.   1154),  Flaischlen 
(Zeits.  f.  Geb.  u.  Oyn.,  1904,  Bd.  li.,  Heft  3),  and  in  my  book  on  "Uterine  Tumours," 
1901,  p.  88. 


464  THE  NATURAL  HISTORY  OF  CANCER 

The  third  class  comprises  a  large  number  of  cases  in  which,  after  the 
extirpation  of  one  or  both  ovaries  for  cystoma,  cancer  subsequently 
supervened  in  some  other  part  of  the  body. 

Thus,  R.  Morison  has  related  two  instances  of  mammary  cancer 
supervening  in  patients,  who  had  undergone  double  ovariotomy  for 
cystoma  :  in  Poupinel's  case,  mammary  cancer  supervened  after  uni- 
lateral ovariotomy,  and  Pfannenstiel  has  reported  a  similar  instance. 

Butler-Smythe  has  seen  cancer  of  the  cervix  uteri  develop  in  a 
patient,  who  had  undergone  double  ovariotomy  for  cystomata,  many 
years  previously ;  and  Morestin  the  same  disease,  after  unilateral 
ovariotomy  for  cystoma. 

Similarly,  many  instances  have  been  reported  of  cancer  of  the  stomach 
and  intestines,  supervening  after  ovariotomy  for  cystomata. 

In  his  work  on  "  Ovarian  Tumours,"  Spencer  Wells  gives  a  table, 
showing  the  subsequent  history  of  all  those  who  recovered  after  com- 
pleted ovariotomy,  for  cystoma.  It  was  found  that  117  had  since  died, 
the  causes  of  death  being  unknown  in  29.  Of  the  remaining  88,  no  fewer 
than  32  had  succumbed  to  cancer,  that  is  to  say,  1  in  2-75.  During  the 
same  period,  the  cancer  mortality  in  the  general  population,  among 
women  of  about  the  same  age,  was  1  in  15. 

Thus,  the  cancer  mortality  was  nearly  five  and  a  half  times  greater  for 
those,  one  or  both  of  whose  ovaries  had  been  extirpated  ;  than  for  those 
who  had  undergone  no  such  operation. 

Of  these  32  cancer  cases,  in  19  the  seat  of  the  disease  is  not  stated, 
in  3  it  was  peritoneal,  in  3  uterine,  in  2  in  the  pedicle,  in  2  rectal ;  and  in 
the  lung,  liver  and  kidney,  each  in  1  case. 

The  date  after  ovariotomy,  at  which  death  from  cancer  supervened, 
is  stated  in  29  cases  ;  10  died  in  the  first  year,  10  in  the  second,  4  in  the 
third,  and  5  at  later  periods. 

In  none  of  the  foregoing  cases  was  there  any  reason  to  suspect,  at 
the  time  of  ovariotomy,  that  malignant  disease  was  then  present. 

In  6  of  the  32  operations,  it  is  distinctly  stated  that  both  ovaries  were 
removed. 

I  have  purposely  omitted  from  this  estimate  four  cases,  in  which 
malignant  disease  supervened  at  very  brief  intervals  after  the  operation  ; 
but,  these  may  well  have  been  instances  of  acute  traumatic  malignancy 
caused  by  the  operation,  such  as  we  occasionally  see  in  other  parts  of  the 
body,  after  operative  procedures  for  the  removal  of  non-malignant 
tumours. 

In  short,  the  cumulative  evidence  of  modern  experience  shows,  that 
the  supervention  of  malignant  disease  is  of  exceptional  frequency,  after 
X  operations  of  this  kind  ;  and  Kratzenstein  *  has  collected  a  hundred 
examples  of  it,  without  having  exhausted  the  records. 

Some  authors  have  endeavoured  to  account  for  the  frequency  of 
cancer  after  ovariotomy  for  cystoma,  by  alleging  that  these  cystomata 
are  really  often  malignant  tumours.  Such  an  opinion  is,  I  believe, 
erroneous,  for  the  following  reasons  : — (1)  It  is  in  direct  conflict  with  the 
mortality  statistics  of  this  country,  and  of  all  countries  where  reliable 
1  Zeitschr.  f.  Geb.  u.  Gyn.,  Bd.  xxxvi.,  S.  61. 


RECURRENCE  465 

records  are  kept,  which  show  that  primary  malignant  disease  of  the  ovaries 
is  decidedly  rare — much  rarer  than  it  would  be  if  this  explanation  were 
correct ;  *  (2)  the  information  furnished  by  the  statistical  records  of  large 
hospitals,  where  cases  of  this  kind  are  carefully  scrutinized,  and  where  a 
considerable  proportion  are  submitted  to  post-mortem  examination,  is 
entirely  in  accord  with  that  derived  from  the  national  statistics;  (3)  more- 
over, during  ovariotomy  and  at  the  examination  of  the  tumour  after  its 
removal,  no  signs  of  malignancy  could  be  detected  in  any  of  the  cases 
included  in  Spencer  Wells'  list. 

If  further  evidence  as  to  the  correctness  of  my  views  on  this  matter 
is  required,  plenty  is  forthcoming. 

Ovariotomy  for  cystoma,  is  not  the  only  abdominal  operation  after 
which  malignant  disease  often  develops.     A  very  large  number  of  cases 
have  now  been  recorded,  showing  the  frequency  of  the  supervention  of 
malignant  disease  after  removal  of  functional  ovaries,  for  various  morbid  )( 
conditions. 

Thus,  after  amputation  of  the  uterus,  together  with  the  ovaries  and 
adnexa,  for  myoma  of  the  uterus,  many  instances  of  the  subsequent 
supervention  of  cancer  have  been  reported,  e.g.,  18  by  Schenk,  11 
by  Schauta,  8  by  Sanger,  5  by  Savor,  and  a  great  many  by  other 
authors. 

Similarly,  after  double  castration  for  various  morbid  (non-ovarian)  / 
conditions,  cancer  has  often  been  known  to  eventuate,  e.g.,  cancer  of  the 
uterus,  two  years  after  the  removal  of  both  ovaries  and  tubes  for  pyo- 
salpinx  (Playfair)  :  uterine  cancer  eight  years  after  double  oophorectomy 
for  myomata  (Blacker)  ;  sarcoma  of  uterus,  many  years  after  removal 
of  both  ovaries  for  myomata  (H.  Spencer)  ;  cancer  of  cervix  of  uterus, 
three  years  after  removal  of  both  ovaries  for  dysmenorrhoea  (Herman) 
etc. 

From  the  foregoing  considerations  it  follows,   that  damage  to  the 
ovaries  by  disease,  or  their  removal  by  operation,  greatly  increases  the     > 
proclivity  to  cancer. 

Of  like  import  is  the  series  of  cases  reported  by  Neugebauer,2  illus- 
trating the  proneness  to  malignant  and  other  tumours,  of  persons  witli 
rudimentary,  badly  developed  or  absent  ovaries — to  which  list  many 
cases  have  since  been  added. 

The  great  frequency  of  cancer  in  castrated  animals,  to  which  I  have 
previously  referred,  also  points  in  the  same  direction. 

Thus,  then,  may  we  explain  the  special  proclivity  to  cancer,  manifested 
by  patients  who  have  undergone  ovariotomy  for  non-malignant  cystoma. 


Rationale  of  Recurrence. 

Returning  now  from  this  digression  to  our  rationale  of  recurrence, 
careful  examination  of  recurrent  malignant  growths  has  revealed  the 
important  fact,  that  in  their  morphological  and  other  characters,  they 
closely  resemble  the  primary  neoplasm.  From  this  we  may  infer,  that 

1  For  the  precise  figures,  vide  Chapter  XII. 

2  Cent.  f.  Qyn.,  1890,  No.  18,  p.  1. 

30 


466  THE  NATURAL  HISTORY  OF  CANCER 

they  originate  from  the  latter  or  its  derivatives  ;  or  that  both  spring  from 
a  similar  matrix.  These  are,  in  fact,  the  sole  sources  of  recurrent 
growths. 

Here  reference  may  be  made  to  the  fact  that  recurrent  growths,  like 
metastases,  do  sometimes  differ  somewhat  from  their  primaries  :  thus 
Heinbaum  l  has  described  an  instance  of  melano-sarcoma  of  the  corneo- 
scleral  junction,  which  recurred  in  situ  after  local  excision,  as  leuco- 
sarcoma  ;  while,  in  a  case  of  leuco-sarcoma  of  the  sclerotic,  treated  in  the 
same  manner,  with  freedom  from  return  of  the  disease  for  seven  years, 
the  malady  then  recurred  in  its  former  site,  as  melano-sarcoma. 

Very  significant  is  it,  that  the  great  majority  of  recurrences  are 
situated  either  in,  or  in  the  immediate  vicinity  of,  the  operation  wound. 
In  the  case  of  mammary  cancer,  the  researches  of  Volkmann,  Heidenhain, 
and  others,  have  conclusively  demonstrated,  that  fragments  of  the 
original  disease  are  almost  invariably  left  behind  after  operations  under- 
taken for  its  removal,  as  hitherto  usually  practised. 

After  the  removal  of  uterine  cancer,  even  by  total  hysterectomy, 
Leopold,  Mackenrodt,  and  others,  have  shown  that  unextirpated  frag- 
ments of  the  disease  are  frequently  left  behind. 

It  seems  certain  that  morbid  fragments  of  this  kind,  persisting  after 
operation,  are  the  germs  whence  most  recurrent  growths  originate. 
Thus  may  be  explained  the  initial  multiplicity  of  most  recurrences,  wherein 
they  differ  so  markedly  from  independent  spontaneous  outgrowths, 
which  are  almost  invariably  solitary. 

The  great  frequency  of  recurrence  soon  after  operations,  points  in  the 
same  direction.  Hence  we  may  conclude,  that  the  immense  majority  of 
local  recurrences  are  due  to  incomplete  ablation  of  the  primary  growth. 
In  these  cases,  there  is,  indeed,  no  real  reproduction  of  the  disease  ;  but 
merely  continuation  of  it,  in  the  surviving  unextirpated  fragments 
(continuation  recurrence). 

Similarly,  when — after  operation — the  disease  recurs  in  adjacent 
lymph-glands,  or  in  remote  parts  of  the  body — apparently  unaffected 
before — we  may  infer  that  its  recrudescence  in  these  situations  is  generally 
due  to  the  dissemination  there  of  seminium  of  the  primary  disease,  prior 
to  the  operation  for  its  removal,  which  have  subsequently  developed,  as 
in  the  formation  of  other  disseminative  growths. 

It  seems  not  improbable  that  some  of  these  local  recurrences  are  due 
to  inoculation  of  the  operation  wound  with  cancer  elements,  detached  by 
the  surgeon's  knife  etc.  To  avoid  this,  Donitz,  Sabatier  and  others, 
recommend  that  care  should  be  taken  not  to  cut  into  such  neoplasms 
during  their  removal. 

There  yet  remain  for  consideration  those  instances  of  late  recurrence, 
appearing  several  years  after  operation — of  which  I  have  previously 
described  several  instances — which  cannot  be  explained  in  this  way, 
without  resorting  to  the  gratuitous  assumption,  that  cancer  elements 
may  lie  dormant  in  the  tissues  for  several  years,  and  then  suddenly 
recover  their  morbid  activity.  Such  cases — which  are  rare — are,  I  think, 
undoubtedly  due  to  independent  outbreaks  of  the  disease  (repullulation) , 
1  Arch.  f.  Augenheilk.,  Ed.  xxxvii.,  Heft  1. 


RECURRENCE  467 

in  unextirpated  remains  of  the  structures  of  the  part  in  which  the  disease  • 
originated. 

This  explains  the  usual  localization  of  late  recurrences  in  the  primarily    ^ 
affected  region,  rather  than  elsewhere  ;  and  their  more  frequent  appear- 
ance in  the  vicinity  of  the  operation  wound,  rather  than  in  the  cicatrix. 

I  have  elsewhere  x  directed  special  attention  to  the  occurrence  in 
the  mammary  region,  its  vicinity  and  the  axilla,  of  detached  fragments 
of  redundant  mammary  glandular  structures,  whence  various  malignant 
and  benign  tumours  may  arise. 

I  have  also  reported  several  instances  of  late  recurrent  cancer,  arising 
from  these  aberrant  structures  ;  and  no  doubt  a  certain  proportion  of  late 
recurrences,  after  radical  thorough  operations,  habitually  originate  thus. 

Similarly  we  may  ascribe  the  origin  of  certain  late  recurrences,  which 
occasionally  form  after  abdominal  total  extirpation  of  the  cancerous 
uterus — when  it  is  hardly  conceivable  that  any  unextirpated  remains  of 
the  uterine  mucosa  or  its  glands  could  possibly  have  been  left  behind — 
to  aberrant  "  rests  "  of  Wolffian  or  Miillerian  structures,  which — as  recent 
researches  have  shown — abound  in  the  para-uterine  tissues  and  their 
vicinity. 

There  still  remain,  however,  certain  exceptional  instances  of  late 
recurrence  at  a  distance,  which  are  not  satisfactorily  explained  by  the 
foregoing  hypothesis  ;  such,  for  instance,  as  Fisher  and  Box's  case,  in 
which  a  pigmented  intra-ocular  cancer  reappeared  in  the  liver,  fourteen 
years  after  extirpation  of  the  eye  for  the  primary  disease  etc. 

In  such  cases  it  seems  probable  that  seminium,  derived  from  hyper- 
plastic,  pre-cancerous  elements  of  the  original  tumour-matrix,  and  trans- 
ported to  the  liver  etc.,  have  subsequently  acquired  in  their  new  habitat 
cancerous  properties.  In  like  manner,  cancer  is  sometimes  seen  to  arise 
primarily  in  the  glands  of  the  groin,  in  association  with  pre-cancerous 
lesions  of  the  penis  and  scrotum,  as  I  have  previously  mentioned.  The 
origin  of  cancer  from  non-malignant  elements,  detached  and  implanted 
in  the  track  of  wounds  made  for  the  removal  of  ovarian  cystoma,  uterine 
myoma  etc.,  long  after  recovery  from  the  completed  operation,  are  pheno- 
mena of  similar  import. 

I  certainly  think  this  explanation  is  more  in  accord  with  the  known 
facts,  than  the  alternative  hypothesis  of  latent  cancer  germs,  which  has 
no  definitely  ascertained  facts  to  rest  on. 

In  a  general  way,  it  is  to  the  processes  of  regeneration  and  repair,  that 
we  must  look  for  the  physiological  prototypes  of  recurrence  ;  just  as  Hydra 
regenerates  itself  after  mutilation,  and  after  it  has  been  cut  into  small 
pieces,  so  it  is  with  these  malignant  tumours. 

1  "  Diseases  of  the  Breast,"  189-1. 


30—2 


CHAPTER  XXI 
CACHEXIA 

AFTER  a  cancerous  growth  has  existed  for  a  variable  time,  which  is  gener- 
ally rather  long,  the  patient's  health  begins  to  suffer — even  in  the  absence 
of  ulceration,  haemorrhage  etc.  Pallor,  weakness,  emaciation  and  loss  of 
appetite,  are  among  the  most  obvious  manifestations.  These,  as  the 
disease  progresses,  become  greatly  aggravated — the  pallor  taking  on  a 
peculiar  earthy,  or  straw-coloured  tint — while  other  indications  of 
profound  disturbance  of  the  general  nutrition  arise  ;  which,  when  the 
malady  runs  its  natural  course,  eventually  determine  death  from 
asthenia. 

The  condition  thus  briefly  sketched,  is  that  generally  known  as  the 
cancerous  cachexia  ;  which,  as  I  shall  proceed  to  show,  depends  upon 
the  entry  into  the  circulation,  of  products  resulting  from  the  disintegra- 
tion of  the  constituent  cells  of  the  cancerous  tumours. 

Cachexia  is  more  frequently  seen  with  malignant  epithelial  tumours, 
than  with  sarcomata  ;  and  in  some  varieties  of  both  types  of  malignant 
disease — such  as  rodent  ulcer,  spindle-celled  and  myeloid  sarcoma — it 
seldom  occurs.  Even  among  the  different  varieties  of  the  same  type  of 
malignant  disease,  there  are  great  divergencies  as  to  the  occurrence  of 
cachexia  ;  thus,  it  is  much  more  frequently  met  with  in  association  with 
cancers,  whose  constituent  cells  are  specially  prone  to  degenerative 
disintegration — such  as  the  ordinary  acinous  cancer  of  the  breast — than 
with  those  whose  cellular  elements  are  more  stable — such  as  epider- 
moidal  cancer  of  the  lower  lip.  Yet  some  destructive  metamorphoses 
of  cancer  cells,  such  as  the  colloid,  are  not  attended  with  cachexia  ;  as 
is  specially  seen  in  the  mammary  form  of  this  disease. 

Moreover,  cachectic  symptoms  are  sometimes  induced  by  very  large, 
non-malignant  tumours,  especially  those  of  ovarian  and  uterine  origin ; 
and  even  by  such  quasi-malignant  pseudo-plasms  as  mycosis  fungoides. 

Similarly,  in  the  constitutional  changes  coincident  with  pregnancy 
and  post-partum  conditions,  we  see  manifested  physiological  counter- 
parts of  cachexia.  Hence,  there  is  nothing  specific  of  cancer  about  it. 

The  condition  certainly  cannot  be  attributed  to  the  mere  abstraction 
of  nutritive  materials  from  the  blood,  as  some  have  suggested  ;  for,  it 
is  often  met  with  in  its  most  marked  form,  in  association  with  quite 
small  cancerous  tumours.  Neither  can  it  be  ascribed  to  septicaemia  ; 
for,  it  appears  to  be  quite  independent  of  such  external  lesions,  as  usually 
accompany  the  ordinary  septic  infections  ab  extra  ;  moreover,  there  is 

468 


CACHEXIA  469 

usually  no  pyrexia,  but  the  temperature  tends  rather  to  be  subnormal  ; 
and,  after  death,  none  of  the  usual  signs  of  septicaemia  are  noticeable. 

It  is  noteworthy  that  cachectic  symptoms  never  precede  the  out- 
break of  the  primary  disease  ;  from  this  we  may  infer,  that  they  are  a 
consequence  of  its  local  progress.  Certain  it  is,  that  after  removal  of 
the  disease  by  operation,  the  cachectic  symptoms  usually  disappear  ; 
and,  in  the  absence  of  recurrence,  patients  may  retain  their  healthy 
appearance  for  several  years,  as  in  cases  I  have  observed.  The  degree 
of  cachexia  is,  however,  by  no  means  always  proportionate  to  the  mere 
extent  of  the  local  malady  ;  for,  I  have  seen  well-marked  cachectic 
symptoms  supervene  acutely,  at  an  early  stage,  when  the  primary 
disease  has  been  quite  small.  Neither  can  it  be  maintained,  that  cachexia" 
is  dependent  upon  dissemination  ;  for,  it  may  be  absent,  when  the  latter 
is  very  marked,  and  vice  versa.  Just  so  it  is  with  regard  to  haemorrhage, 
which  affects  only  a  minority  of  cancer  cases.  In  certain  exceptional 
instances,  the  disease  may  even  run  its  entire  course,  without  ever 
causing  any  cachexia,  or  other  very  obvious  disturbance  of  the  general 
nutrition,  the  patients  being  able  to  follow  their  usual  avocations  almost 
to  the  last.  Indeed,  cancer  patients  seldom  take  to  bed,  until  the 
disease  has  run  more  than  half  its  course. 

Weakness  is  a  much  later  symptom  of  this  condition  than  emacia- 
tion ;  and  anaemia  generally  goes  before  the  latter.  The  precise  date  at 
which  cachectic  symptoms  are  most  prone  to  supervene,  their  sequence 
and  degree  ojE  development  are,  however,  so  variable  ;  that  detailed 
general  statements  respecting  them  cannot  usefully  be  made. 

We  may,  I  think,  best  interpret  these  symptoms,  as  the  result  of  a 
general  toxaemia,  the  explanation  of  which  must  be  sought  in  the  remark- 
able proneness  of  the  constituent  cells  of  cancers  to  undergo  degenerative 
changes,  which  are  often  so  extreme  as  to  lead  to  their  complete  destruc- 
tion by  disintegration.  When  such  excrementitious  products  find  their 
way — by  nutritive  absorption  or  otherwise — into  the  general  circulation, 
in  quantities  too  great  to  be  quickly  eliminated  and  destroyed,  they 
poison  the  fluids  of  the  body  ;  and  so,  by  a  kind  of  auto-intoxication, 
similar  to  that  by  which  the  system  is  infected  from  an  inflammatory 
focus,  they  originate  the  phenomena  of  the  cancerous  cachexia.  It 
seems  probable,  that  the  excrementitious  products  thus  derived  contain 
toxic  albuminoids,  analogous  to  the  virulent  substances  secreted  by 
microbes.  Through  these  agencies  the  haematopoietic  organs — especially 
the  lymphatic  apparatus — are  injuriously  affected.  Thus  the  blood  of 
cancer  patients  gets  profoundly  modified,  both  qualitatively  and 
quantitatively.  The  red  blood-corpuscles  show  signs  of  progressive 
deterioration  and  destruction,  while  the  white  ones  become  much  more 
numerous. 

There  is,  however,  nothing  specific  about  these  changes,  which  are 
similar  to  those  met  with  in  other  anaemic  states. 

It  was  long  ago  shown  by  Andral x  and  Simon  that,  in  cancer  patients, 
the  red  corpuscles  of  the  blood  are  greatly  diminished  in  numbers — even 
in  the  absence  of  ulceration  and  haemorrhage — and  these  results  have 
1  "Essai  d'Hematol.  path.,"  1843,  p.  175. 


470  THE  NATURAL  HISTORY  OF  CANCER 

been  confirmed  by  recent  investigators  (Hayem  and  others).  Thus, 
while  the  number  of  red  corpuscles  in  a  cubic  millimetre  of  a  healthy 
woman's  blood  is  about  4,500,000,  in  cancer  patients — even  during  the 
early  stages  of  the  disease  —  the  number  present  is  often  less  than 
3,000,000 ;  and — at  subsequent  stages — it  may  descend  to  1,000,000,  or 
even  lower. 

In  healthy  women,  the  proportion  of  reds  to  whites  is  about  750 
to  1  ;  but  in  those  with  cancer  the  ratio  varies  from  380 — 60  to  1. 

In  pernicious  anaemia,  the  diminution  in  the  number  of  red  corpuscles 
is  much  greater  than  in  cancer — viz.,  to  1,500,000  or  even  300,000  per 
cubic  millimetre. 

Various  alterations  in  the  form  of  the  red  corpuscles  are  also  met 
with  in  the  blood  of  the  cancerous,  most  of  which  are  indicative  of 
degenerative  changes  (e.g.,  microcytes  and  poikilocytes).  Hayem 
maintains  that  the  pseudo-parasitic  bodies  found  in  the  blood  by  several 
observers,  are  mostly  due  to  conditions  of  this  kind  (fragmentation  etc.). 
Probably  the  minute,  highly  refractile,  amoeboid  bodies — found  by 
Kahane,  in  the  freshly  drawn  blood  etc.  of  cancer  patients — may  also 
be  of  this  nature  ;  as  well  as  Niessen's  mycete,  which  he  regards  as 
specific.  To  enable  us  to  appreciateThe  worth  of  these  and  other  alleged 
cancer  microbes  in  the  blood,  we  need  to  be  better  informed  than  we  are 
at  present,  as  to  the  organisms  that  may  be  found  in  the  blood  in  health 
and  disease. 

In  pernicious  anaemia,  similar  degenerative  changes,  of  an  even  more 
marked  character,  are  of  common  occurrence, 

Bord  and  Kullmann  claim  to  have  found  a  haemolysin  in  the  blood  of 
cancerous  patients,  which  they  think  may  be  utilized  for  diagnostic 
purposes. 

Nucleated  red  globules  (normoblasts)  and  megaloblasts,  are  of  rare 
occurrence  in  most  forms  of  cancer,  but  common  in  pernicious  anaemia  ; 
on  the  other  hand,  blood-plates  (haematoblasts  of  Hayem)  are  fairly 
numerous  in  cancer — except  in  advanced  stages  of  the  disease — whereas, 
in  pernicious  anaemia,  these  bodies  are  greatly  reduced  in  numbers, 
falling  from  300,000  per  cubic  millimetre — the  normal — to  less  than 
25,000. 

The  poverty  of  the  blood  of  cancer  patients  in  haemoglobin,  has 
been  demonstrated  by  Quinquaud1:  1,000  grammes  of  normal  blood 
contain  about  125  grammes  of  this  substance  ;  whereas,  in  cancer  cases, 
the  amount  often  does  not  exceed  25  grammes.  The  investigations  of 
Bierfrund  and  others  are  to  the  same  effect. 

The  difference  between  cancerous  and  non-cancerous  blood  in  this 

respect  is  so  marked  and  constant,  that  Laker 2  maintains  it  may  be 

relied  on  for  the  purpose  of  differential  diagnosis.     Marked  diminution 

4  of  haemoglobin  may  be  detected,  even  before  any  deterioration  in  the 

patient's  general  health  is  noticeable. 

In  pernicious  anaemia,  the  haemoglobin  is  also  diminished  ;  but  in  a  less 
degree  than  might  be  expected,  considering  the  great  deglobulization. 

1  "TraitS  technique  de  chimie  biologique,"  etc.,  Paris,  1883. 

2  Cent.  f.  d.  med.  Wissenschaft,  1887,  S.  405. 


CACHEXIA  471 

The  immediate  effect  of  injecting  physiological  or  microbic  poisons 
into  the  circulation  is,  as  Lowit l  has  shown,  to  cause  sudden  and  rapid 
decrease  in  the  number  of  leucocytes  in  the  blood  (leucolysis),  the  vascular 
intoxication  at  first  causing  their  destruction.  If  the  animal  survive, 
however,  marked  regenerative  leucocytosis  soon  sets  in,  the  increase 
being  chiefly  of  the  lymphocytes  from  the  irritated  lymphoid  tissue. 

Leucolysis  has  never  been  demonstrated  in  connexion  with  the 
cancerous  toxaemia  ;  but,  the  condition  being  a  fleeting  one,  may  never- 
theless occur. 

Marked  increase  in  the  number  of  the  white  corpuscles — leucocytosis 
— is  the  rule  in  advanced  cancer  ;  but,  in  early  stages  of  the  disease,  this 
condition  is  usually  lacking — especially  in  cancer  of  the  stomach.  Hayem  2 
found  the  number  of  leucocytes  increased  from  6,000  per  cubic  millimetre 
— the  normal  standard — to  17,600,  in  certain  cases  of  cancer  of  the 
stomach  ;  to  11,400  in  breast  cancer  ;  to  7,800  in  uterine  cancer  ;  and 
much  higher  counts  have  been  met  with. 

Similar  conditions  have  been  demonstrated,  in  connexion  with 
sarcomatous  tumours. 

Very  remarkable  diminution  of  leucocytosis  has  been  noted,  after 
the  extirpation  of  mammary  cancer  :  in  one  case  the  leucocyte-count, 
which  was  21,700  before  operation,  fell  to  6,200  soon  afterwards  ;  but, 
with  the  advent  of  recurrence,  it  steadily  rose  again.  Hayem  considers 
that  by  enumerating  the  leucocytes,  the  on-coming  of  recurrence  can  be 
predicted,  before  any  other  physical  signs  thereof  are  noticeable. 

In  cases  complicated  by  metastasis,  leucocytosis  is  almost  invariable, 
especially  when  the  osseous  system  is  affected. 

Many  of  the  foregoing  changes  remind  us  of  the  effects  produced 
on  the  blood,  by  such  drugs  as  pyradine,  which  cause  destruction  of  the 
red  globules,  with  increase  of  the  white  ones. 

In  a  general  way,  leucocytosis  is  regarded  by  pathologists,  as  a  re- 
action of  the  organism  to  counteract  some  injurious  toxaemia  ;  but,  as 
to  whether  the  increased  production  of  leucocytes  is  due  to  stimulation 
of  those  organs  which  produce  them  (Virchow  and  Ehrlich),  or  to 
chemiotaxic  influence  at  the  site  of  the  lesion  (Limbeck  and  Jakob),  is 
still  undecided. 

The  precise  role  of  each  of  the  different  varieties  of  leucocytes,  in  the 
leucocytosis  of  cancer,  has  not  yet  been  satisfactorily  determined.  Sur- 
geons have  hitherto  taken  but  little  interest  in  such  matters  ;  and  progress 
is  also  impeded  by  uncertainty,  as  to  the  origin  and  development  of 
leucocytes.  According  to  Ehrlich,  leucocytes  with  granulations  originate 
in  bone-marrow,  and  persist  in  original  type  throughout  life  ;  while  non- 
granular,  large  and  small  lymphocytes,  are  formed  in  lymph-glands,  and 
then  passed  into  the  circulation.  Other  pathologists  consider  that 
leucocytes  are  developed  from  small  lymphocytes,  in  lymph-glands  and 
bone-marrow,  by  a  process  of  "  ripening  "  in  the  blood-stream  ;  and  the 
leucocytosis  of  digestion  is  regarded  as  an  indication  favouring  this  view. 
Cabot 3  considers  that,  in  the  leucocytosis  of  cancer,  the  adult  forms  are 

1  "Studien  z.  Physiol.  u.  Path,  des  Blutes  u.  d.  Lymphe,"  Jena,  1892. 

2  "Du  Sang,"  Paris,  1889.  3  "Clinical  Examination  of  the  Blood,"  1897. 


472  THE  NATURAL  HISTORY  OF  CANCER 

unduly  augmented,  at  the  expense  of  the  immature  cells.  Generally, 
however,  this  form  of  leucocytosis  is  found  to  be  due  to  augmentation  in 
the  number  of  lymphocytes,  which  are  believed  to  be  produced  in  excess 
by  the  irritated  lymphatic  organs  ;  nearly  as  frequently,  however,  the 
polynuclear  leucocytes  (neutrophile  of  Ehrlich),  which  normally  comprise 
from  62  to  70  per  cent  of  all  leucocytes,  are  the  ones  chiefly  augmented. 
It  has  been  determined  by  Zappert  *  and  others,  that  the  eosinophile 
)( corpuscles  are  decidedly  diminished  in  numbers  in  cancer  patients, 
probably  being  attracted  from  the  blood  to  the  seat  of  disease,  where 
they  are  retained,  as  after  various  experimental  traumata  ;  but,  with 
regard  to  the  mono-nuclear  basophiles  or  mast  cells,  beyond  the  fact  that 
they  are  met  with  in  cancer,  nothing  has  yet  been  definitely  ascertained. 

Myelocytes,  which  are  not  one  of  the  normal  constituents  of  the 
vf  blood,  are  found  in  cancer  more  frequently  than  in  any  other  diseases, 
except  pernicious  ansemia  and  leukaemia,  although  the  percentage  is 
usually  only  small. 

In  pernicious  anaemia  there  is  no  leucocytosis ;  indeed,  the  leuco- 
cytes may  be  much  reduced  in  numbers,  even  to  1,500  per  cubic  milli- 
metre. 

The  most  marked  changes  in  the  blood  in  cancer,  are  those  seen  in 
cases  presenting  metastasis,  with  secondary  growths  in  the  bones.  An 
instructive  example  of  this  kind  has  been  recorded  by  Kurpjuweit,2  in 
which  a  woman,  aged  thirty-four,  with  cancer  of  the  pylorus,  and  dis- 
semination in  the  liver,  retro-peritoneal  glands,  and  osseous  system,  was 
found  to  have  the  following  blood  condition  :  the  reds  numbered 
1,825,000,  and  the  haemoglobin  amounted  to  only  25  per  cent. ;  the 
whites  numbered  9,100  ;  comprising  48-4  per  cent,  of  polynuclear  leuco- 
cytes, 11  per  cent,  of  neutrophile  myelocytes,  6-6  per  cent,  of  tran- 
sitional forms  between  the  foregoing,  12-2  per  cent,  of  large  lymphocytes, 
19-2  per  cent,  of  small  lymphocytes,  1-6  per  cent,  of  eosinophile  cells,  and 
1  mast  cell  in  2  preparations.  Here,  the  myelocytosis  pointed  con- 
clusively, to  implication  of  the  bone-marrow.  There  was  also  myeloid 
metaplasia  of  the  liver,  spleen,  lymph-glands  and  medulla  of  the  bones, 
indicating  the  abnormal  activity  of  these  structures  in  regenerating  the 
deficient  blood  elements.  Kurpjuweit  has  collected  13  cases  of  this 
kind,  in  all  of  which  marked  anaemia  and  myelocytosis  were  associated 
with  metastases  in  the  osseous  system.  It  is  this  type  of  malignant 
disease,  which  occasionally  gives  rise  to  all  —  or  nearly  all  —  of  the 
symptoms  of  pernicious  anaemia,  and  even  of  myelogenous  leukaemia. 

Sarcomatous,  as  compared  with  malignant  epithelial  tumours,  seem 
generally  to  produce  the  more  profound  blood  alterations  ;  they  are 
attended  with  greater  anaemia,  more  pronounced  reduction  of  the  haemo- 
globin, and  a  higher  degree  of  leucocytosis,  than  is  usual  with  epithelio- 
mata. 

In  making  use  of  leucocytosis  for  diagnostic  purposes,  it  must  be 
borne  in  mind  that,  even  in  health,  the  number  of  leucocytes  presents 
considerable  variations.  Thus,  after  a  meal,  it  is  greatly  increased  ; 

1  Zeitschr.  f.  klin.  Med.,  Bd.  xxiii.,  S.  227. 

2  Deutsche  Arch.  /.  klin.  Med.,  1903,  Bd.  Ixxvii.,  Heft  5  and  6. 


CACHEXIA  473 

and  there  is  a  post-haemorrhagic  leucocytosis,  as  well  as  a  leucocytosis 
of  pregnancy,  of  the  newly  born,  and  of  the  dying.  Moreover,  similar 
conditions  accompany  inflammatory  and  febrile  affections. 

Persistent  leucocytosis  with  a  tumour,  unattended  by  inflammation    , 
or  suppuration,  is  generally  due  to  malignant  disease. 

It  has  been  pointed  out  by  Schneyer  l  and  Hartung,2  and  confirmed 
by  others,  that  the  leucocytosis  of  digestion  does  not  occur  in  patients  > 
with  cancer  of  the  stomach  ;  whereas,  it  is  very  noticeable  in  gastric 
ulcer,  pyloric  stenosis,  and  most  other  non-cancerous  conditions.  This 
may  aid  in  distinguishing  the  latter  affections  from  cancer  ;  but  it  must 
not  be  too  implicitly  relied  on. 

Probably  no  disease  can  be  definitely  diagnosed,  on  the  evidence  of 
an  examination  of  the  formed  elements  of  the  blood  alone  ;  and,  on  the 
whole,  the  morphological  peculiarities  of  these  elements,  generally 
furnish  the  most  reliable  indications. 

So  far  as  present  experience  goes,  the  serum  of  cancer  patients  has 
been  found  to  yield  no  agglutin  reaction  ;  nor  has  any  specific  opsonin 
been  detected  in  it. 

The  quantity  of  albumin  and  inorganic  salts  dissolved  in  the  plasma 
is  less  than  the  normal,  according  to  Moraczewski  3  ;  the  phosphorus  is 
notably  diminished,  as  in  all  ansemias,  while  there  is  relative  increase  of 
the  chlorides.  Its  alkalinity  is  also  increased  ;  and  this  is  believed  to  be 
the  cause  of  the  absence  of  free  hydrochloric  acid  from  the  stomach  inV 
gastric  cancer.  Even  under  normal  conditions,  the  body  fluids  are 
believed  to  acquire  increased  alkalinity  with  advancing  age. 

Here  it  may  be  noted  that  there  is  diminution  in  the  gastric  hydro- 
chloric acid,  not  only  in  cancer  of  the  stomach,  but  also  in  almost  all 
cases  of  cancer,  as  well  as  in  various  other  obscure  cachexias.4 

It  is  owing  to  the  poverty  of  the  blood  in  these  and  other  respects — 
especially  to  the  diminution  of  its  haemoglobin — that  its  low  specific 
gravity  (1012  to  1016  in  some  cases  of  gastric  cancer)  is  due. 

On  the  other  hand,  an  excess  of  sugar-forming  matters  is,  according  to    ^ 
Freund,5  of  constant  occurrence. 

Such  states  of  the  blood  explain  the  tendency  in  advanced  cachexia, 
to  passive  serous  effusions  (hydrothorax,  anasarca  etc.)  ;  as  well  as  to 
thrombosis  (e.g.,  of  the  pulmonary  artery,  iliac  veins  etc.),  to  phlebitis, 
to  subacute  congestions  and  inflammatory  affections  of  the  lungs,  to 
petechise,  purpura,  retinal  haemorrhage  etc.  It  is  specially  in  cases  with 
metastases  in  the  bones,  such  as  Kurpjuweit  has  described  ;  and  also  in 
cases  of  general  sarcomatosis,  such  as  Martin,6  Hamilton  and  Fagge 
have  reported,  that  lesions  of  this  type  are  apt  to  occur. 

This  deteriorated  condition  of  the  blood  also  enables  us  to  understand, 
how  it  is  that  great  losses  of  this  fluid  are  repaired  so  much  more 
slowly  in  the  cancerous  than  in  the  non-cancerous,  to  which  Bier- 
frund  has  called  special  attention. 

Not  only  are  the  morphological  and  chemical  constituents  of  the 

1  Munch,  med.  Woch.,  1894,  S.  917.  2   Wien.  med.  Woch.,  1895,  S.  697. 

3  Arch.  f.  path.  Anat.,  Bd.  cxxxix...,  S.  385. 

*  B.  Moore,  Pro.  Roy.  Soc.,  March,  1905.  5   Wien.  med.  Blatter.  1885,  No.  9. 

B  Journal  of  Experimental  Medicine,  1896,  vol.  i.,  p.  595. 


474  THE  NATURAL  HISTORY  OF  CANCER 

blood  thus  altered  ;  but,  as  the  experiments  of  Louis  x  show,  its  total 
^quantity  is  notably  diminished.  Thus  may  be  explained  the  smallness 
of  the  heart,  aorta,  and  arterial  trunks,  in  most  post-mortem  cancer 
cases,  that  have  run  their  natural  course  ;  although,  as  Beneke  has  shown, 
prior  to  the  outbreak  of  the  disease,  cancer  patients  have  large  hearts 
and  bloodvessels  :  and  the  natural  tendency  is  for  the  heart  and  large 
arteries  to  increase  in  size  and  weight  from  childhood  to  old  age,  as  I 
have  mentioned  in  a  previous  chapter.2  It  quite  accords  with  these 
conditions  of  the  circulatory  apparatus,  that  the  cancerous  cachexia 
is  often  associated  with  vascular  hypotension,  as  Janeway  3  has  lately 
indicated. 

One  of  the  most  obvious  manifestations  of  this  depraved  state  of  the 
blood,  is  pallor  of  the  skin  ;  which,  as  the  disease  progresses,  often  assumes 
a  waxy,  puffy,  aspect,  together  with  the  peculiar  straw-coloured  tint  so 
characteristic  of  the  cancerous  cachexia.  There  is,  however,  nothing 
specific  about  it ;  for  a  similar  condition  is  met  with  in  other  anaemic 
states,  especially  in  chlorosis  and  in  pernicious  anaemia.  It  is  probably 
due  to  altered  haemoglobin,  taken  up  by  the  plasma  of  the  blood. 

A  later  developed  manifestation  is  emaciation  ;  which  when  it  has  once 
set  in,  is  steadily  progressive,  so  that  the  wasting  is  often  extreme.  This, 
like  most  of  the  other  individual  symptoms  of  the  cancerous  cachexia, 
may,  however,  occasionally  be  absent. 

As  the  disease  progresses  weakness  appears,  and  increases  pari  passu. 
4p  Gastro-intestinal  disturbance  is  commonly  experienced.  Loss  of 
appetite,  dyspepsia,  anorexia,  together  with  thirst,  are  often  prominent 
symptoms.  Nausea  and  vomiting  are  also  of  frequent  occurrence,  even 
in  the  absence  of  visceral  dissemination  ;  and  slight  jaundice  is  not  un- 
common. Constipation  oftener  exists  than  diarrhoea  ;  and  aversion  to 
nitrogenous  food  is  frequently  met  with. 

It  has  lately  been  suggested  by  Copeman,  that  many  of  these 
symptoms  are  consequent  on  the  chyme,  which  enters  the  duodenum 
from  the  stomach  after  a  meal,  being  insufficiently  acid  to  stimulate  an 
adequate  amount  of  pancreatic  secretion. 

V  Quasi-rheumatic  pains  in  various  parts  of  the  body,  remote  from  the 
primary  seat  of  disease,  such  as  the  loins,  hips,  lower  limbs  etc.,  are  often 
complained  of.  When  these  coincide  with  subacute  febrile  disturbance, 
as  occasionally  happens,  the  condition  may  easily  be  mistaken  for  sub- 
acute  rheumatism,  of  which  I  have  seen  several  instances.  Often  pains 
of  a  neuralgic  character  are  experienced  ;  as  well  as  numbness  and 
tingling  of  the  hands  and  feet ;  and  an  undue  impressionability  to  cold 
may  be  noticeable. 

Those  who  have  examined  cancer  patients  for  peripheral  neuritis 
have  often  found  it— e.g.,  Isch-Wall,4  Auche,5  Gombault,  Klippel  etc. 

Various  symptoms  also  arise  owing  to  disturbance  of  the  sympa- 

*•  thetic  nervous  system  ;  among  these  I  have  frequently  observed  alternate 

flushing  and  pallor  of  the  face  and  hands — sometimes  so  marked  as  to 

1  "  Researches  on  Phthisis  "  (Walshe's  translation),  1846,  p.  52. 

2  Chapter  XVI.  3  «  Blood  pressure,"  1904,  p.  237. 

Cancer  et  Arthritisme,"  These  de  Paris,  1890,  No.  147. 
"  Des  nevrites  peripheriques  chez  les  cancereuses,"  Rev.  de  Med.,  1890,  p.  785. 


CACHEXIA  475 

suggest  Raynaud's  disease — cardiac  palpitation,  syncope,  tachycardia, 
shortness  of  breath  and  gastric  disturbance.  I  can  also  testify  as  to  the 
correctness  of  Bogdan's  1  observation  ;  that  red  patches  are  frequently 
visible  on  the  cheeks,  owing  to  dilatation  of  the  superficial  bloodvessels. 
These  vaso-motor  disturbances  are  most  marked  in  intra-abdominal 
cancers  (e.g.,  of  the  stomach  and  uterus).  Other  observers  (Cuffer, 
Riehl  etc.)  have  described  various  visceral  vaso-motor  disturbances, 
which  they  attribute  to  inflammation  of  the  sympathetic  nerves.  Her- 
petic  and  erythematous  eruptions  are  also  occasionally  seen. 

In  the  course  of  the  disease,  cancer  patients  are  apt  to  become  irritable 
and  depressed  ;  but  I  have  not  noticed  any  special  tendency  to  morose- 
ness,  on  which  Lebert  insists.  Headache  and  insomnia  are  of  frequent 
occurrence  ;  but  the  mind  usually  remains  clear  to  the  last. 

In  a  few  cases,  after  the  disease  has  existed  for  a  considerable  time, 
cancer  patients  become  insane  ;  the  form  of  mental  derangement  I  have 
most  frequently  seen  is  that  of  dementia.  Pinel  2  mentions  a  case  of 
this  kind,  in  which  the  insanity  was  cured  by  removal  of  the  cancerous 
disease.  Other  nerve  effects  of  cancer  have  also  been  noted,  such  as 
hyper-excitability  of  the  muscles,  increased  reflexes,  defective  co-ordina- 
tion, reaction  of  degeneration  ;  with  mild  delirium,  coma  etc.,  in  ad- 
vanced cases.  In  connexion  with  symptoms  of  this  kind,  various  minute 
lesions  of  the  brain,  spinal  cord  and  meninges  have  been  reported  by 
Sanger,3  Lubarsch,4  Klippel,6  and  others,  which  have  their  counterparts 
in  other  severe  anaemias. 

A  condition  resembling  diabetic  coma — the  coma  carcinomatosum — is 
occasionally  met  with,  of  which  Jaksch  6  has  made  a  special  study. 

Alterations  in  the  blood,  that  involve  considerable  reduction  in  its 
haemoglobin,  as  in  phthisis,  anaemia  etc.,  are  usually  associated — after  a 
time — with  widespread  fatty  degeneration,  the  result  of  impaired  oxidation 
Irom  diminished  supply  of  oxygen.  The  cancerous  cachexia  is  no  excep- 
tion to  this  rule.  The  parts  most  obviously  thus  affected,  I  have  found 
to  be,  the  liver,  aortic  arch,  kidneys,  large  arteries,  heart  etc. ;  but  micro- 
scopical examination  shows  that  similar  changes  are  almost  universal. 
The  anorexia  and  constipation  so  frequently  met  with,  are  largely  due 
to  changes  of  this  kind,  affecting  the  liver  and  the  gastro-intestinal 
mucosa.7  I  have  found  that  the  liver  is  more  frequently  thus  affected, 
in  an  extreme  degree,  than  any  other  organ  ;  it  happened  thus  in  17  out 
of  my  44  breast-cancer  necropsies,  and  in  21  out  of  my  78  uterine-cancer 
necropsies. 

From  the  general  malnutrition  consequent  on  the  cancerous  toxaemia, 
the  bones  suffer  as  well  as  the  other  structures.  Great  interest  attaches 
to  these  little  studied  changes,  which  require  to  be  carefully  discriminated 
from  the  lesions  produced  by  cancerous  dissemination,  with  which  most 
pathologists  have  confounded  them.  According  to  my  experience,  the 

Bull,  de  la  Soc.  des  Med.,  etc.,  de  Jassy,  1894. 
Traite  de  Path.  Cerebrale,  p.  224. 
Neurologische  Centralblatter.  December  1,  1901. 

Zeitschr.  f.  klin.  Med.,  Bd.  xxxi.,  S.  389.  6  Arch.  gen.  de  Mid.,  January,  1899. 

Wien.  med.  Woch.,  1883,  Bd.  xxxiii.,  S.  473  and  521. 
Fenwick,  Medico-Chirurgical  Transactions,  London,  vol.  xlviii.,  p.  267. 


476  THE  NATURAL  HISTORY  OF  CANCER 

bones  most  frequently  thus  affected  in  a  marked  degree  are  the  ribs, 
sternum,  femur,  cranial  bones,  humerus,  and  vertebrae.  These,  when 
affected,  still  retain  their  normal  size  and  shape  ;  but  they  are  lighter 
and  more  fragile  than  they  should  be,  so  that  they  are  easily  fractured. 
Campbell's  l  interesting  experiments  show,  that  their  breaking  strain  is 
very  low  indeed — often  even  four  times  less  than  the  normal.  There  is 
X  thinning  of  the  cortex,  with  increased  size  of  the  medullary  canal,  the 
cancelli  and  Haversian  canals  being  much  enlarged  and  filled  with 
diffluent  medulla,  hence  the  undue  porosity.  The  ends  of  the  long 
bones  are  specially  apt  to  be  affected  in  this  way.  Altogether  the  indi- 
cations point  to  defective  deposition  of  new  bone  to  replace  the  loss  by 
absorption,  as  the  proximate  cause  of  the  condition. 

Somewhat  similar  skeletal  changes  have  been  observed  in  many 
chronic  wasting  diseases,  in  the  insane,  in  the  aged,  in  pregnant  women, 
in  chronic  phosphorus-poisoning  etc. 

v  Owing  to  this  fragility  of  the  bones,  spontaneous  fractures  are  easily 
determined — in  the  absence  of  any  cancerous  dissemination  ;  of  this  I 
have  met  with  several  instances.2 

It  seems  probable  that  the  affection  is  in  some  way  connected  with 
alterations  in  the  blood-forming  properties  of  the  red  marrow  ;  and  it  is 
a  fact,  that  the  bones  most  frequently  thus  affected  are  just  those  in  which 
haematopoietic  functions  are  normally  most  active.  In  this  form  of 
mollities,  I  have  often  noticed  that  the  medulla  has  a  gelatinous,  diffluent 
aspect,  very  different  from  its  normal  appearance.  According  to  Villy  3 
and  others,  there  is  increase  of  the  red  marrow  at  first,  with  disappearance 
of  the  fat  cells  ;  and  subsequently  gelatinous  degeneration  supervenes. 
Somewhat  similar  changes  have  been  produced  experimentally  in 
animals,  by  repeated  bleedings  ;  and  in  pernicious  anaemia  analogous 
conditions  occur. 

According  to  Rommelacre,4  F.  Miiller5  and  others,  the  amount  of 
X  urea  in  the  urine  of  cancer  patients,  is  decidedly  below  the  normal, 
independently  of  alimentation,  indicating  lessened  excretion  of  nitro- 
genous matter,  owing  to  the  great  demands  on  the  albuminous  con- 
stituents of  the  body  for  the  manufacture  of  new  cells. 

While  the  nitrogen  distribution  of  normal  urine  comprised  96  per 
cent,  urea,  1-8  per  cent,  uric  acid,  1-2  per  cent.  NHg,  and  0-6  to  0-8  per 
cent,  extractives,  Topfer  found  that  the  nitrogen  of  the  urine  of  cancer 
patients  comprised  less  than  80  per  cent,  urea,  1  to  5  per  cent,  uric  acid, 
0-2  to  13  per  cent.  NH3,  and  13  to  23  per  cent,  extractives. 

The  most  constant  of  this  group  of  changes  seems  to  be  the  relative 
increase  of  the  nitrogen  of  the  extractives. 

Most  investigators  report  that  the  excretion  of  nitrogen  in  cancer 
.    patients  is  much  in  excess  of  the  amount  taken  with  the  food  ;  and  the 
like  is  also  alleged  of  the  mineral  salts. 

1  British  Medical  Journal,  1895,  vol.  ii.,  p.  776. 

For  details  and  references  to  other  cases  of  this  kind,  vide  my  book  on  <;  Diseases 
of  the  Breast,"  1894,  p.  215. 

3  Journal  of  Pathology  and  Bacteriology,  January,  1898,  p.  69  :  and  May,  p.  229. 

*  J.  de  Med.  de  BruxeUes,  1883-1884. 

5  Zeitschr.  f.  klin.  Med.,  1889,  Bd.  xvi.,  S.  496. 


CACHEXIA  477 

According  to  some  authors  there  is  relative  increase  of  uric  acid  ; 
but  this  is  seldom  a  marked  feature,  and  it  is  often  wanting. 

Another  feature  of  the  urine  of  the  cancerous  is  its  progressive  de- 
mineralization,  especially  in  respect  to  chlorides  and  phosphates.  Noorden 
maintains  that  this  diminution  of  chlorides  is  due  to  lessened  intake  of 
sodic  chloride  ;  and  according  to  some  authors  the  phosphates  may  be 
unaltered  or  even  increased. 

F.  Miiller  reports  having  found  slight  degrees  of  albuminuria  of 
common  occurrence  in  the  cancerous  ;  and  albumoses  may  also  be  met 
with. 

An  excess  of  acetone  has  been  noticed  by  Argenson  and  others ; 
while  Lewin l  has  found  its  aromatic  substances  notably  increased  ; 
and  F.  Miiller  an  augmentation  of  the  urobilin. 

Gaudier  and  Hilt  have  lately  shown,  that  the  urine  of  the  cancerous 
is  more  toxic  than  normal  urine  ;  and,  in  operated  cases,  they  have  found 
that  this  toxicity  disappeared,  after  the  removal  of  the  local  disease. 
Meyer2  comes  to  the  same  conclusion  ;  and  finds  also  that  the  splenic 
substance  is  highly  toxic  ;  while  Griffiths  3  claims  to  have  isolated  from 
the  urine  of  cancerous  patients  a  highly  poisonous  ptomaine,  not  present 
in  normal  urine. 

A  remarkable  fact  that  may  be  mentioned  here,  is  the  rarity  with 
which  amyloid  degeneration  is  associated  with  cancer  ;  among  my  44 
breast-cancer  necropsies  there  was  not  a  single  instance  of  it,  and  it  was 
met  with  only  in  4  cases,  out  of  my  78  uterine-cancer  necropsies.  In 
each  of  these  instances,  the  spleen  was  involved,  and  in  2  the  liver  as 
well. 

It  is  now  generally  recognized,  that  suppuration  and  ulceration  are 
not  essential  precursors  of  amylosis,  which  may  ensue  from  a  variety  of 
morbid  conditions  that  seriously  interfere  with  nutrition — e.g.,  chronic 
intermittent  fevers,  malarial  cachexia,  large  uterine  and  ovarian  tumours, 
rachitis,  gout  etc. 

In  this  connexion,  great  interest  attaches  to  Krawkow's  experiments, 
on  the  artificial  production  of  amylosis,  by  the  injection  of  cultures  of 
Staphylococcus  pyogenes  aureus  ;  whence  the  author  concludes,  that  the 
amyloid  material  is  a  result  of  the  constant  poisoning  and  lowering  of 
the  organism  by  microbic  products. 

The  comparative  rarity  and  the  slight  intensity  of  the  febrile  com- 
plications of  cancer,  is  a  noteworthy  feature  of  the  disease  ;  but,  occa- 
sionally fever  is  found,  independently  of  ulceration  or  of  any  inflam- 
matory process,  just  as  sometimes  happens  after  simple  fracture  of  a 
long  bone.  In  such  cases,  it  may  be  ascribed  to  some  deleterious  sub- 
stance entering  the  circulation — in  the  one  case  from  the  tumour,  in  the 
other  from  the  damaged  tissues — and  subsequently  affecting  the  heat 
centre,  so  as  to  cause  fever. 

Fever  is  specially  apt  to  be  met  with  in  cancer  cases,  complicated  by 
intra-osseous  metastases. 

1  Deutsche,  med.  Woch.,  1905,  Bd.  xxxi.,  S.  218. 

2  Zeitschr.  /.  Uin.  Med.,  Bd.  xxxiii.,  S.  663. 

3  C.  R.  de  I'Acad.  des  Set.,  Paris,  t.  cxviii.,  p.  1350. 


478  THE  NATURAL  HISTORY  OF  CANCER 

When  cancerous  growths  ulcerate  and  the  wounds  are  invaded  by 
microbes,  the  ordinary  symptoms  of  septic  infection  are  added  to  those 
of  the  cancerous  cachexia.  Considering  the  putridity  that  characterizes 
these  ulcerating  cancers,  especially  when  the  uterus  is  the  part  affected, 
septic  complications  are  remarkably  rare  ;  but,  no  doubt,  in  certain 
cases,  they  contribute  their  quota  to  the  ensemble  of  symptoms. 

Haemorrhages  and  suppurations  further  impoverish  the  blood,  and 
weaken  the  patient. 

At  length,  if  not  cut  off  by  some  inter-current  complication,  death 
results  from  asthenia  :  it  was  thus  that  64  of  90  uterine-cancer  cases, 
that  ran  their  natural  course  under  my  observation,  terminated  ;  and, 
in  24  of  40  fatal  cases  of  breast  cancer,  the  end  was  similarly  determined. 

It  will  be  gathered  from  the  foregoing  review,  that  no  indications  of 
a  specific  cancer  toxin  are  forthcoming  :  altered  conditions  of  the  blood, 
secondary  diseases  of  the  organs  which  play  an  important  part  in 
metabolism,  diminished  intake  of  food,  superadded  microbic  infections 
etc.,  suffice  to  account  for  all  such  changes  as  have  hitherto  been  dis- 
criminated. 


CHAPTER  XXII 
QUASI-MALIGNANT  PSEUDO-PLASMS 

THE  enterprise  of  modern  surgery,  with  its  frequent  exploratory  opera- 
tions from  which  no  part  of  the  body  is  exempt ;  the  greater  frequency 
and  thoroughness  of  modern  post-mortem  examinations  ;  the  increasing 
accuracy  of  death  certification,  with  corresponding  improvement  in  the 
national  mortality  statistics ;  and  finally,  the  wonder  caused  by  the  immense 
number  of  reputed  "  cures,"  of  all  kinds,  for  cancer — duly  attested  by 
skilled  practitioners  and  specialists,  with  histological  verification  etc.,  etc. 
— although  those  best  capable  of  judging  doubt  if  a  single  case  of  cancer 
has  ever  been  really  cured  :  all  these  concomitant  events  have  at  length 
revealed  to  practitioners  the  truth,  long  known  to  those  who  have  specially 
studied  the  disease,  that  the  differential  diagnosis  of  cancer  is  a  difficult 
matter,  in  which  mistakes  are  of  frequent  occurrence. 

Having  arrived  at  this  conclusion,  the  question  naturally  arises  as 
to  the  chief  causes  of  these  diagnostic  fallacies.  In  a  general  way,  they 
may  no  doubt  be  ascribed  to  the  fact,  that  there  is  no  pathognomonic 
sign  of  cancer  ;  nor  does  the  disease  produce  any  specific  symptoms, 
indicative  of  its  presence.  Hence,  every  case  has  to  be  judged,  by  care- 
fully weighing  the  ensemble  of  the  indications  available  for  diagnostic 
purposes.  To  do  this  effectually,  a  much  more  intimate  acquaintance 
with  the  pathology  and  life-history  of  cancer  is  required,  than  is  at 
present  possessed  by  practitioners — whether  holding  hospital  appoint- 
ments or  not ;  and,  it  is  equally  important,  to  be  keenly  alive  to  the 
many  morbid  conditions  which  simulate  cancer,  as  to  which  practitioners 
have  also  almost  everything  to  learn. 

The  sources  of  these  diagnostic  fallacies  may  be  divided  roughly  into 
two  classes  : — (1)  those  very  numerous  cases  in  which  cancer  is  simulated 
by  some  non-malignant  morbid  condition  ;  and  (2)  a  smaller  class  of  cases, 
in  which — owing  to  the  latency  or  misleading  nature  of  the  symptoms — 
the  presence  of  the  malady  is  overlooked. 

It  is  with  the  former  group  of  cases,  that  we  are  here  chiefly  con- 
cerned. Owing  to  the  immense  extent  of  the  subject,  it  will  be  impossible 
in  the  brief  space  available,  to  do  more  than  direct  attention  to  this  order 
of  fallacies,  by  some  general  observations  relating  thereto,  coupled  with 
reference  to  a  few  typical  illustrative  instances. 

As  a  rule,  the  chief  non- malignant  morbid  conditions  likely  to  simulate 
cancer,  may  be  grouped  as  follows  : — (1)  many  "  chronic  inflammatory  " 
affections  ;  (2)  various  syphilitic  lesions  ;  (3)  a  very  large  number  of 
tuberculous  manifestations  ;  (4)  many  mycotic  affections  ;  (5)  various 

479 


480  THE  NATURAL  HISTORY  OF  CANCER 

parasitic  and  microbic  lesions  ;  and  (6)  a  large  class  of  pseudo-parasitic 
maladies,  of  which  the  causative  agent  is  unknown  or  only  dimly  appre- 
hended. 

The  professional  mind  is  so  obsessed  with  the  erroneous  idea  that  any 
tumour,  not  obviously  inflammatory,  appearing  in  persons  over  forty, 
is  almost  invariably  malignant ;  that  further  exploration  of  its  nature  is 
seldom  seriously  undertaken.  This  is  specially  noticeable,  in  the  case 
of  tumours  of  the  female  breast ;  indeed,  a  prominent  cancer  surgeon 
lately  stated  his  belief,  that  every  tumour  of  the  breast  in  women  over 
forty,  "  whether  cyst,  fibroma  or  what  not,"  sooner  or  later  underwent 
"  malignant  degeneration,"  and  so  required  extirpation  forthwith.  As 
I  have  previously  adduced  evidence  to  show,  such  a  belief  has  no  scientific 
validity,  although  it  may  be  very  convenient  for  surgeons.  The  truth 
is,  that  of  100  women  seeking  surgical  advice,  on  account  of  tumour- 
like  swellings  of  the  breast  believed  to  be  malignant,  it  will  be  found  that 
less  than  half  of  the  total  are  really  of  this  nature. 

Of  the  pseudo-cancerous  lesions,  the  largest  proportion  will  un- 
doubtedly prove  to  be  "  chronic  inflammatory  "  indurations.  By  far 
the  commonest  manifestation  of  this  kind  likely  to  be  mistaken  for 
cancer,  is  the  chronic  circumscribed  mastitis — the  induratio  benigna  of 
the  old  authors.  I  have  seen  several  instances  in  which  this  condition 
has  been  mistaken  for  cancer,  and  the  breast  amputated  ;  and  illus- 
trative specimens  of  this  kind  may  be  found  in  most  pathological  museums. 

In  a  case  under  my  own  observation,  the  patient  was  a  large,  obese 
woman,  aged  fifty-seven,  the  mother  of  two  children,  with  a  lump  in  her 
left  breast  of  seven  years'  duration.  The  breasts  were  voluminous. 
Near  the  periphery  of  the  axillary  segment  of  the  affected  part,  was  a  very 
hard,  nodulated  mass,  the  size  of  a  tangerine  orange,  covered  by  a  thick 
layer  of  fat.  The  overlying  skin  was  adherent  and  dimpled  ;  but  the 
tumour  was  movable  over  the  subjacent  parts,  and  the  nipple  was  normal. 
There  was  no  pain  or  tenderness.  Several  axillary  glands  were  enlarged. 
An  exploratory  incision  into  the  tumour,  revealed  a  dense,  whitish 
fibroid  aspect,  just  like  that  of  ordinary  scirrhous  cancer.  Even  after  its 
complete  removal,  the  aspect  of  the  divided  tumour  was  very  cancer- 
like  ;  but  the  section  did  not  "  cup,"  and  it  was  juiceless.  Histological 
examination  showed  dense  fibrous  tissue,  containing  numerous  nuclei, 
in  which  a  few  acinous  and  tubular  mammary  glandular  structures  were 
embedded  :  but  there  were  no  signs  of  cancer.  The  enlarged  axillary 
glands  were  also  free  from  cancer.  When  last  seen,  three  years  after  the 
operation,  this  patient  was  in  excellent  health,  and  free  from  any  return 
of  the  disease. 

Here  the  unusual  absence  of  pain  and  tenderness,  together  with  the 
presence  of  dimpling  of  the  skin,  and  all  the  usual  signs  of  cancer  except 
retraction  of  the  nipple,  prevented  the  recognition  of  the  real  nature  of 
the  disease,  although  the  chronicity  of  the  lesion  excited  doubt  as  to  its 
cancerous  nature. 

Even  various  inert  foreign  bodies,  embedded  in  the  breast,  such  as 
needles,  pins,  bits  of  glass,  small  sequestra  from  the  subjacent  ribs,  which 
have  separated  by  quiet  necrosis  etc.,  may  give  rise  to  chronic  indurations, 


QUASI-MALIGNANT  PSEUDO-PLASMS  481 

simulating  cancer.  There  is  a  specimen  of  this  kind  in  the  Hunterian 
Museum,  presented  by  Astley  Cooper  (No.  67  of  the  Pathological  Series), 
which  is  thus  described  :  "  Part  of  a  woman's  breast  removed  on  account 
of  what  was  supposed  to  be  a  chronic  tumour.  A  needle  2  inches  long 
is  embedded  in  the  mammary  gland,  the  surrounding  substance  of  which 
is  indurated  :  the  needle  is  covered  with  rust,  but  is  in  other  respects 
perfect." 

Another  form  of  chronic  mastitis,  likely  to  be  mistaken  for  cancer,  is 
the  diffuse,  cirrhosing  variety,  which  produces  retraction  of  the  nipple 
and  overlying  skin,  with  wasting  and  deformity  of  the  part,  similar 
to  that  characteristic  of  atrophic  scirrhus. 

Periductal  mastitis,  the  maladie  noueuse  of  French  authors,  the 
plexiform  fibroma  of  the  Germans,  and  the  "  lobular  hypertrophy  "  of 
English  writers,  which  is  generally  attended  with  sclerosing  fibrosis, 
often  simulates  cancer,  although  less  frequently  than  the  foregoing 
types. 

It  is  a  common  mistake  of  clinicians  to  suppose,  that  tuberculous 
lesions  of  the  female  breast  are  of  exceptional  rarity  ;  they  are  really  of 
commoner  occurrence  than  is  generally  believed  ;  and,  when  in  the  form 
of  chronic  indurations,  and  as  cold  abscesses,  they  are  often  mistaken 
for  cancer. 

By  way  of  illustration,  the  two  following  remarkable  cases  are  of 
exceptional  interest  : — 

1.  I  was  requested  by  a  medical  friend  to  see  an  unmarried  lady, 
aged  forty,  with  a  swelling  in  her  breast  of  some  months'  duration,  which 
she  attributed  to  an  accidental  blow  from  a  child's  elbow.  On  examina- 
tion, I  found  near  the  periphery  of  the  axillary  part  of  her  left  breast, 
a  nodular  lump,  the  size  of  a  marble,  surrounded  by  irregular,  ill-defined 
thickening  and  induration.  Although  the  lump  was  hard,  yet  the 
degree  of  induration  seemed  to  me  to  fall  short  of  that  usually  associated 
with  scirrhous  cancer.  The  tumour  was  painful,  and  on  manipulation 
decidedly  tender.  The  nipple  was  stunted  and  transversely  grooved  ; 
but,  both  were  alike  in  these  respects,  and  neither  was  retracted.  The 
skin  over  the  tumour  was  decidedly  drawn  upon,  so  that  when  a  cutaneous 
fold -was  pinched  up  it  dimpled  ;  but  the  tumour  was  movable  on  the 
subjacent  parts.  The  adjacent  axillary  glands  were  enlarged.  I  also 
detected  slight  lobular  thickening  in  the  opposite  breast.  The  patient 
had  chronic  cough,  with  a  small  amount  of  muco-purulent  expectoration, 
and  moist  rales  could  be  heard  over  the  upper  lobe  of  her  left  lung.  In 
early  adult  life,  she  had  haemoptysis  ;  and  subsequently,  for  many  years, 
active  phthisical  disease.  Some  years  ago,  however,  this  became  qui- 
escent ;  and  her  general  health  subsequently  greatly  improved.  Three 
of  her  sisters  had  died  of  phthisis.  Under  these  circumstances — relying 
mainly  on  the  pain  and  tenderness  of  the  swelling,  the  comparative 
rapidity  of  its  formation,  its  ill-defined  margins  and  moderate  hardness, 
as  well  as  on  the  slight  lesions  in  the  opposite  breast — I  was  able  to 
assure  the  patient  that  the  tumour  was  almost  certainly  not  cancerous. 
Moreover,  relying  on  the  presence  of  tuberculous  disease  in  the  lungs, 
and  the  history  of  it  in  her  family,  I  expressed  the  opinion  that  in  all 

31 


482  THE  NATURAL  HISTORY  OF  CANCER 

probability  the  mammary  lesion  was  also  of  tuberculous  origin  ;  and 
recommended  local  and  general  anti-tuberculous  treatment. 

I  was  then  for  the  first  time  informed,  that  the  lady  had  previously 
consulted  a  medical  man  elsewhere,  who  had  pronounced  her  disease 
to  be  cancerous  ;  and  had  made  every  arrangement  for  amputating  the 
breast  the  following  week.  I  consequently  sent  this  gentleman  a  polite 
note,  stating  the  circumstances,  and  what  I  had  recommended.  He 
wrote  a  huffy  letter  to  the  patient's  friends,  making  light  of  my  diagnosis 
and  suggestions  for  treatment,  recommending  that  the  operation  should 
nevertheless  be  proceeded  with  as  arranged,  and  deprecating  the  painful 
predicament  in  which  the  patient  was  placed.  Fortunately,  this  advice 
was  not  followed  ;  and,  after  a  few  months'  treatment,  the  disease  entirely 
disappeared. 

2.  At  the  Pitie  Hospital  in  Paris,  I  witnessed  the  following  instructive 
case,  in  which  a  tuberculous  abscess  was  mistaken  for  cancer  of  the 
breast  : — 

A  healthy  -  looking  multipara,  aged  thirty,  applied  to  Verneuil  on 
account  of  a  mammary  tumour  of  six  months'  duration,  which  she  first 
noticed  about  a  month  after  her  last  confinement.  On  examination, 
there  was  found,  deeply  seated  in  her  left  breast,  an  exceedingly  hard, 
irregularly  shaped  mass,  about  the  size  of  an  orange.  At  one  spot  the 
tumour  was  softer  than  elsewhere,  and  gave  indications  of  indistinct 
fluctuation.  The  adjacent  axillary  glands  were  enlarged.  The  nipple 
was  not  retracted,  nor  was  the  overlying  skin  dimpled  ;  and  there  was 
only  slight  pain  and  tenderness.  Basing  his  remarks  on  this  case,  the 
learned  professor  gave  to  the  assembled  class  an  eloquent  address,  on 
the  differential  diagnosis  of  mammary  cancer,  with  special  reference  to 
its  discrimination  from  cold  abscess.  He  concluded,  from  the  extreme 
hardness  of  the  tumour,  and  the  enlargement  of  the  axillary  glands, 
that  the  case  before  them  was  an  undoubted  example  of  scirrhus,  although 
some  of  the  usual  clinical  features  were  wanting.  In  accordance  with 
this  view,  he  proceeded,  before  the  whole  class,  to  amputate  the  breast 
with  the  thermo-cautery  knife.  In  the  middle  of  the  operation,  a  large 
abscess  cavity  was  opened,  out  of  which  gushed  a  considerable  quantity 
of  thick  yellow  pus.  The  eloquent  professor  looked  grave  and  puzzled. 
He  proceeded  with  his  operation,  however,  including  removal  of  the 
axillary  glands.  The  patient  made  a  complete  and  rapid  recovery. 
Subsequent  histological  examination  of  the  parts  removed,  showed  no 
signs  of  cancer  ;  but  all  the  indications  of  a  cold,  tuberculous  abscess. 

It  would  be  easy  to  multiply  such  cases  as  the  foregoing  ;  and  cancer- 
like  lesions,  due  to  pseudo-tuberculosis  of  this  part,  have  often  been 
reported. 

I  have  not  the  slightest  doubt,  that  a  certain  proportion  of  these 
quasi-malignant  indurations  of  the  female  breast,  are  of  syphilitic  origin  ; 
I  have  seen  cases  of  this  kind,  in  which  the  affection  took  the  form  of 
gummatous  tumour,  and  others  in  which  it  was  of  a  more  or  less  infil- 
trating nature. 

In  making  the  diagnosis  of  the  various  non-malignant,  tumour-like 
lesions,  likely  to  be  mistaken  for  cancer,  some  surgeons,  and  notably 


QUASI-MALIGNANT  PSEUDO-PLASMS  483 

Bryant,1  attach  great  importance  to  cysts.  According  to  my  investiga- 
tions, cysts  rarely  originate  in  the  breast,  independently  of  neoplasia  ; 
that  is  to  say,  cysts  of  sufficient  size  to  require  notice,  in  respect  to  the 
question  of  the  differential  diagnosis  of  cancer.  An  analysis  I  have  made 
of  2,397  mammary  tumours,  consecutively  under  treatment  at  four 
large  metropolitan  hospitals,  shows  that  only  63  were  cysts,  or  2-6  per 
cent. 

Certain  cysts,  especially  when  tense  and  deeply  seated — like  cold 
abscesses — occasionally  acquire  stony  hardness,  and  otherwise  simulate 
cancer  ;  but,  such  cases  are  far  from  common.  For  one  such  cyst  re- 
sembling cancer,  at  least  a  dozen  tumour-like  swellings  of  inflammatory 
origin  (chronic  mastitis,  tubercle,  syphilis,  cold  abscess  etc.),  easily  mis- 
takable  for  cancer,  will  be  met  with.. 

With  regard  to  the  discrimination  from  malignant  disease  of  fibro- 
adenoma,  villous  papilloma,  the  effects  of  trauma — including  foreign 
bodies  embedded  in  the  part,  galactocele,  and  slight  glandular  thicken- 
ings associated  with  neuralgia  etc. — nothing  further  than  the  mere 
mention  of  such  contingencies  is  here  necessary. 

The  numerous  cases  of  actmomycosis  in  human  beings,  reported 
during  the  last  quarter  of  a  century,  show  that  this  disease  is  by  no  means 
rare  in  mankind  ;  and,  almost  every  part  of  the  body,  has  been  found 
affected.  Over  a  score  of  cases  of  this  kind  have  already  been  reported 
in  the  breast,  in  some  of  which  the  symptoms  of  malignant  disease  were 
closely  simulated  ;  so  that,  in  making  the  diagnosis  of  quasi-malignant 
tumours,  this  malady  has  also  to  be  borne  in  mind. 

A  few  cases  of  mammary  mycosis  fungoides,  having  much  resemblance 
to  sarcoma,  have  also  been  reported  (Lancereaux,  Leslie  Roberts  etc.). 

Even  small,  tense,  hydatid  cysts,  which  are  decidedly  rare  in  the 
breast,  have  been  mistaken  for  cancer. 

Under  a  variety  of  curious  names  of  their  own  special  invention, 
which  serve  as  a  cloak  for  their  lack  of  understanding  of  the  pathology 
of  the  maladies,  dermatologists  have  brought  together  a  chaotic  medley 
of  quasi-malignant  cutaneous  pseudo-plasms,  which  are  constantly  mis- 
taken for  true  malignant  tumours. 

A  large  number  of  these  seem  to  be  the  outcome  of  tuberculous  disease, 
in  some  of  its  protean  forms,  most  of  them  belonging  to  the  lupus  family, 
with  its  many  aberrant  variations. 

The  "  epithelioma-like  "  histological  appearances  of  sections  of  lupus- 
ulcers,  was  long  ago  demonstrated  by  Lang,  Busch  and  others  ;  but, 
these  histological  findings,  do  not  justify  the  diagnosis  of  "  cancer." 

When,  however,  the  lupus  -  malady  departs  from  its  ordinary 
course,  producing  chronic  carneous  excrescences  ;  then,  such  histological 
findings,  are  thought  to  justify  the  diagnosis  of  "  lupus-cancer,"  as 
in  cases  reported  by  Bayha  and  others.  From  such  an  interpretation 
I  entirely  dissent ;  and,  in  the  absence  of  clinical  signs  of  malignancy,  I 
believe  that  such  lesions  would  be  more  correctly  described  as  lupus 
hypertrophicus.  Certainly,  they  have  no  real  similitude  with  any  form 
of  epithelioma  or  sarcoma. 

1  Lancet,  1900,  vol.  i.,  p.  1201. 

31—2 


484  THE  NATURAL  HISTORY  OF  CANCER 

Another  malady  belonging  to  a  kindred  category,  is  the  sarcoma 
melanodes  cutis  (Kaposi's  disease),  in  which  multiple  "  sarco-carcino- 
matous  "  nodes  form  on  the  face  or  other  exposed  parts  of  the  body, 
often  in  quite  young  children,  more  than  one  member  of  a  family  often 
being  affected. 

It  seems  to  me  an  abuse  of  terms  to  describe  such  a  malady  as  sar- 
coma, on  account  of  certain  histological  appearances  of  sections  of  the 
tumour  ;  when  the  ensemble  of  the  indications  available  for  diagnostic 
purposes  point  in  quite  another  direction. 

A  good  many  cases  of  multiple,  quasi-malignant  pseudo-plasms  of 
the  skin,  have  also  been  described  as  "  sarcoma,"  because  round,  spindle, 
or  myeloid  cells  have  predominated  in  their  structure  :  this  type  of 
disease  fairly  often  undergoes  more  or  less  complete  resolution — either 
spontaneously,  or  as  the  result  of  various  remedial  agencies — and  is 
otherwise  about  as  unlike  any  form  of  real  sarcoma,  as  any  malady  could 
possibly  be.  Most  of  such  tumours  are  probably  of  tuberculous,  or 
mycotic  origin. 

As  examples  of  this  morbid  condition  reference  may  be  made 
to  a  case  described  by  S.  Mackenzie,1  in  which  a  man  aged  fifty- 
four,  was  subject  to  livid  nodular  growths  on  the  hands  and  feet,  which 
on  histological  examination  presented  a  sarcoma-like  appearance — 
"  multiple  pigmented  sarcoma."  Four  years  after  amputation  of  the 
right  leg  for  this  malady,  the  remaining  lesions  spontaneously  retrogressed 
and  disappeared. 

In  R.  Crocker's  case,2  a  man  aged  thirty-seven  who  had  suffered 
for  some  time  from  arthritic  troubles,  developed  a  number  of  small 
crimson  tumours  on  the  hands,  head,  back  and  other  parts,  which 
rapidly  increased  in  size.  Nearly  a  year  later,  when  the  patient  was 
taking  salicylate  of  soda  for  the  arthritic  condition,  these  tumours  began 
to  dwindle,  and  finally  most  of  them  disappeared.  The  histological 
appearances  of  sections  of  the  tumours,  resembled  myeloid  sarcoma. 

Other  cases  of  this  kind  have  been  described  by  Kobner,3  Kaposi  etc., 
as  examples  of  cutaneous  sarcomatosis  ;  by  Shattock  and  Ballance  4  as 
"withering  sarcoma";  by  Cotterill  and  Welsh5  as  "  syphiloma  ";  by 
Bristowe  6  as  "  tubercle  ";  and  by  many  authors  as  "  granuloma  fun- 
goides,"  "  lymphadenie  cutanee"  etc. 

"  Duhring's  neoplasm,"  in  which  fungating  growths  like  tomatoes 
form  in  the  skin,  some  of  which  shrivel  and  disappear  from  time  to  time, 
while  new  ones  arise,  should  probably  be  classed  in  the  same  category  ; 
for,  the  ensemble  of  the  malady  is  entirely  different  from  true  sarcoma, 
with  which  it  has  hitherto  been  confounded.  As  Duhring 7  himself 
says  :  "  Better  let  it  be  named  and  unclassified,  than  be  placed  and 
become  fixed  wrongly." 

Somewhat  similar  fungating  tumours,  some  of  which  undergo  spon- 
taneous resolution,  also  occur  in  that  interesting  malacly  mycosis  fun- 
Lancet,  1896,  vol.  ii.,  p.  470.  2  Ibid. 
Berlin,  klin.  Woch.,  1883,  No.  2. 


Allbutt's  "System  of  Medicine,"  1896,  vol.  i.,  p.  215. 

'ves  of  Dermatology,  January,  1880. 


British  Medical  Journal,  1900,  vol.  ii.,  p.  1444.^ 
Ibid.,  1892,  vol.  ii.,  p.  996.  7  Archive. 


QUASI-MALIGNANT  PSEUDO-PLASMS  485 

goides,  which  is  so  often  confused  with  sarcoma.  These  growths  are 
almost  certainly  of  microbic  origin,  although  no  specific  organism  has 
yet  been  detected. 

This  is  the  class  to  which 'the  so-called  "withering  sarcomata" 
belong  ;  which  are  so  often  cited,  as  evidence  of  the  curability  of  sarcoma. 

Quite  lately  the  important  discovery  has  been  made,  that  certain 
blastomycetes,  oidia  etc.,  are  capable  of  causing  quasi-sarcomatous  lesions 
of  this  kind,  as  well  as  chronic  cutaneous  ulcers,  like  epithelioma.  We  owe 
this  discovery  chiefly  to  the  experiments  of  Sanfelice  and  his  followers, 
although  Busse  and  Curtis  had  previously  reported  remarkable  instances 
of  the  kind  in  human  beings,  as  mentioned  in  a  previous  chapter,1 
and  I  particularly  recommend  that  these  cases  should  be  carefully  studied 
in  the  present  connexion  ;  for,  in  all  probability,  many  of  these  quasi- 
malignant,  cutaneous  pseudo-plasms  are  thus  caused. 

Granulomatoue,  cutaneous  pseudo-plasms,  simulating  malignancy, 
due  to  mould  fungi  aspergillosis,  coccidiosis,  botryomycosis  etc.,  have 
also  been  reported. 

Actinomycotic,  quasi-malignant,  tumour-like  lesions  of  the  skin, 
have  also  been  demonstrated  in  many  cases. 

Quasi-epitheliomatous  ulcers  of  the  skin,  often  resembling  rodent 
ulcer,  due  to  tubercle,  syphilis,  chronic  seborrhcea,  and  mycotic  lesions, 
are  no  great  rarities  ;  and  these  are  the  cases  that  the  X  rays  cure. 

Moreover,  there  can  be  no  doubt  that  quasi-cancerous  lesions  of  the 
skin,  are  often  caused  by  atypical  syphilitic  manifestations.  Esmarch  2 
has  specially  shown  us  the  great  frequency  of  lesions  of  this  type  :  thus, 
he  has  had,  in  his  own  practice,  more  than  forty  patients  sent  to  him 
for  operation  with  supposed  malignant  growths,  wliich  subsequently 
underwent  complete  resolution,  under  antisyphilitic  treatment.  The 
special  and  general  medical  publications  teem  with  illustrative  cases 
of  this  kind. 

Even  ordinary  chronic  inflammatory  cutaneous  lesions,  such  as 
"  chronic  seborrhcea,"  may  originate  quasi-malignant,  tumour-like 
swellings  ;  and  it  is  probable  that  the  whole  keloid  group  is  due  to  causes 
of  this  kind. 

Moreover,  it  is  alleged  that  certain  drugs,  such  as  arsenic  and  iodide 
of  potassium — when  unduly  pushed  or  in  cases  of  idiosyncrasy — may 
cause  quasi-malignant,  tumour-like  lesions. 

If  then,  in  parts  of  the  body  so  easily  accessible  to  physical  examina- 
tion as  the  female  breast  and  the  skin,  we  nevertheless  encounter  these 
numerous  sources  of  fallacy,  in  making  the  diagnosis  of  malignant  disease, 
it  may  readily  be  imagined,  how  much  these  difficulties  are  enhanced  in 
parts  less  favourably  situated  for  thorough  exploration,  but  nevertheless 
equally  liable  to  these  quasi-malignant  lesions. 

Some  remarkable  examples  of  quasi-malignant,  disappearing  tumours, 
in  connexion  with  the  stomach,  have  been  reported. 

In  Jessett's3  case,  a  large  tumour  of  this  kind  connected  with  the 
pylorus,  completely  disappeared  after  gastro-enterostomy ;  although, 

1  Chapter  X.          2    Verhandl.  d.  deuteche  QeseUsch.  {.  Chir.,  Kongress,  1895,  Bd.  xxiv. 
3  Lancet,  1901,  vol.  i.,  p.  1005. 


486  THE  NATURAL  HISTORY  OF  CANCER 

when  microscopically  and  microscopically  examined,  it  presented  the 
appearance  of  hard  cancer.  Similar  instances  have  been  met  with  by 
Warthin  and  Spitzley,1  Hasse  2  and  Bennett.3 

Examples  of  quasi-malignant  intestinal  lesions  due  to  tubercle,  have 
been  described  by  Bezangon  and  Lapointe,4  Moynihan  5  etc.  ;  and,  to 
actinomycosis,  by  Borelius  6  etc. 

Some  time  ago  G.  Smith  7  specially  called  attention  to  certain  solid, 
quasi-malignant,  intra-abdominal  tumours,  which  subsequently  under- 
went complete  resolution  ;  and  these  he  showed  were  due  to  chronic 
inflammatory  lesions.  Many  similar  instances  have  since  been  investi- 
gated, with  the  like  result,  although  in  some  there  has  been  a  diagnosis 
of  sarcoma  or  carcinoma,  based  on  histological  findings  :  R.  Johnson,8 
H.  Snow,9  Warthin  and  Spitzley,10  M.  Robson,11  Janeway  12  and  others, 
have  reported  examples  of  this  kind. 

Some  striking  cases  of  these  disappearing,  quasi-malignant  tumours 
in  the  orbit,  have  been  met  with  by  S.  Snell,13  Panas  and  others. 

These  few  typical  examples  suffice  to  show  the  necessity,  for  giving 
more  attention  to  the  differential  diagnosis  of  malignant  disease  in  the 
clinics,  than  has  hitherto  been  customary  ;  and,  no  harm  would  be  done, 
if  it  were  generally  admitted,  that  we  are  still  far  from  knowing  all  that 
is  to  be  known  about  cancer,  even  in  its  clinical  aspect. 

As  I  have  previously  mentioned,  pseudo-plasms  of  the  kind  here  under 
-consideration,  are  of  even  more  frequent  occurrence  in  animals,  than  in 
humanity  ;  and  they  seem  to  attain  their  maximum  of  frequency  in 
fishes.  In  the  vegetable  world,  they  are  also  of  great  frequency,  especially 
in  the  form  of  galls. 

1  New  York  Medical  News,  1901,  vol.  Ixxix.,  p.  443. 

2  Arch.  f.  path.  Anat.,  1897,  Bd.  cxlix.,  S.  236;.also  ibid.,  1896,  Bd.  cxlvi.,  S.  209. 

3  "  Cancerous  and  Canceroid  Growths,"  1849,  pp.  39  and  212. 
*  La  Presse  Ned.,  May  18,  1898. 

5  Transactions  of  the  Clinical  Society  of  London,  1907,  vol.  xl.,  p.  31. 

6  Nord.  Med.  Arkiv.,  1903,  No.  6. 

7  Transactions  of  the  Medico-Chirurgical  Society,  London,  1894,  vol.  Ixxvii.,  p.  139. 

8  British  Medical  Journal,  1903,  vol.  i.,  p.  915. 
Ibid.,  1897,  vol.  i.,    .  1414. 


10  New  York  Medical  News,  1901,  vol.  Ixxix.,  p.  443. 

11  British  Medical  Journal,  1908,  vol.  i.,  p.  425. 
Trans,  of  the  Association  o 

Lancet,  1897,  vol.  i.,  p.  238. 


,          ,        .    .,     .         . 

12  Trans,  of  the  Association  of  American  Physicians,  1907,  vol.  xxii.,  p.  170. 
13 


CHAPTER  XXIII 

INFLAMMATION,  ULCERATION,  RETROGRESSION,  AND 
SPONTANEOUS  CURE 

CANCEROUS  tumours,  once  formed,  live  and  are  nourished  like  normal 
parts  of  the  body  ;  yet  they,  in  return  for  the  nutriment  thus  supplied, 
contribute  nothing  serviceable — functionless  and  redundant,  their  re- 
lationship to  the  rest  of  the  organism,  differs  but  little  from  that  of 
parasitism. 

The  biology  of  cancers,  like  that  of  normal  parts,  is  conditioned  mainly 
by  the  inherent  properties  of  their  constituent  cells  ;  and,  in  a  less  degree, 
by  their  blood-supply.  Hence,  the  same  elementary  pathological  dis- 
turbances may  be  witnessed  in  them,  as  in  the  normal  parts — e.g.,  con- 
gestion, inflammation,  suppuration,  gangrene,  necrobiosis,  ulceration, 
a,nd  the  degenerative  metamorphoses.  That  long-continued  augmenta- 
tion of  the  blood-supply,  may  accelerate  the  growth  of  cancers  ;  and 
diminished  blood-supply  retard  it,  is  I  think  indisputable.  The  marked 
exacerbation  of  mammary  cancers,  consequent  on  pregnancy,  traumata, 
and  various  irritants,  are  examples  of  the  former  effect ;  while  many 
very  chronic  forms  of  the  disease,  are  probably  largely  dependent  upon 
the  latter.  I  am,  however,  far  from  believing  that  most  of  the  striking 
irregularities  in  the  rate  of  growth  of  cancers,  can  be  accounted  for 
by  circulatory  disturbances.  The  inherent  properties  of  the  neoplastic 
cells  themselves,  here  play  the  leading  part. 

The  most  frequent  anatomical  cause  of  congestion  and  inflammation 
of  cancers,  is  obstruction  of  their  venous  circulation,  which,  as  I  have 
previously  mentioned,  so  often  happens  during  the  progress  of  their 
growth  ;  and,  the  defective  formation  of  their  bloodvessels,  no  doubt 
favours  these  conditions. 

Cancers  are,  however,  less  frequently  subject  to  acute  inflammation, 
than  might  a  priori  be  expected.  When  this  does  occur,  not  only  the 
neoplasm  itself,  but  also  its  immediate  surroundings  may  be  affected. 
Such  attacks,  which  are  mostly  of  septic  origin,  often  greatly  accelerate 
the  progress  of  the  disease.  Subacute  inflammations,  are  commoner 
than  the  acute  ones.  Cohnheim  believes  that  inflammatory  conditions 
of  the  surrounding  tissues  weaken  their  capacity  for  resistance,  and  so 
favour  the  spread  of  the  disease.  Inflammation  of  cancer  may  terminate 
in  resolution,  suppuration,  or  gangrene. 

Suppuration  is  rare,  but  it  undoubtedly  does  occur. 

Habermaas  1  has  related  a  curious  case,  in  which  the  breast  was  ampu- 

1  Beitr.  z.  klin.  Chir..  1886,  Bd.  ii.,  S.  44. 

487 


488  THE  NATURAL  HISTORY  OF  CANCER 

tated  for  a  tumour — accompanied  by  enlarged  axillary  glands — which 
was  believed  to  be  tuberculous.  On  examination  of  the  part,  after  re- 
moval, this  diagnosis  appeared  to  be  correct,  for  there  was  revealed  a  pus- 
containing  cavity,  surrounded  by  caseous-looking  masses.  Histologically 
examined,  however,  these  proved  to  be,  not  tuberculous,  but  cancerous. 

Gross  x  mentions  the  case  of  a  woman,  whose  breast  he  had  amputated 
for  a  cancerous  tumour,  the  size  of  a  hen's  egg.  On  section  of  the  growth 
after  removal,  he  found  in  it  an  abscess  full  of  greenish  pus.  H.  Marsh  2 
and  Shield3  have  described  several  cases  of  suppurating  malignant 
tumours.  However,  the  suppuration  of  primary  malignant  tumours 
is  so  exceptional,  that  when  this  condition  is  met  with  in  a  quasi- 
malignant  new  formation,  it  raises  the  presumption  of  mycotic  infection, 
tubercle  or  syphilis,  rather  than  of  cancer. 

Instances  of  the  association  of  mammary  cancer  with  suppurating 
galactocele,  with  tubercle,  and  with  pseudo-tubercle,  have  also  been 
reported. 

A  more  frequent  ending  than  suppuration,  is  gangrene  and  sloughing. 
This  is  generally  only  partial,  but  exceptionally  the  whole  tumour  may 
fall  into  a  state  of  slough. 

Ulcerated  cancers  are  more  prone  to  gangrene  than  others.  Some- 
times the  sphacelus  is  determined  by  injury,  or  by  septic  infection  such 
as  erysipelas  ;  but  usually  there  is  no  obvious  cause. 

Obliteration  of  the  veins  is  its  chief  determining  factor  ;  hence,  it  is 
generally  of  the  moist  kind,  but  the  dry  form  is  not  unknown.  Gangrene 
is  always  a  harmful  complication  ;  severe  local  inflammation  and  pain 
attend  it,  together  with  profuse,  foetid  discharge,  pyrexia  and  much 
constitutional  disturbance  ;  and  the  danger  from  sepsis  is  very  great. 
Gangrene  may  be  followed  by  almost  complete  cicatrization  ;  but,  as 
the  disease  is  never  entirely  destroyed,  recurrence  is  inevitable — at  any 
rate,  I  cannot  cite  a  single  instance  of  cure  by  gangrene. 

For  the  following  account  of  a  case,  in  which  a  cancerous  breast 
separated  by  sloughing,  consequent  on  erysipelas,  I  am  indebted  to  Dr. 
Richmond  of  Warrington. 

A  single  woman,  aged  forty-five,  had  scirrhous  cancer  of  the  left 
breast,  and  cancerous  glands  in  the  axilla.  While  waiting  for  extirpa- 
tion, a  sharp  attack  of  erysipelas  supervened,  involving  the  diseased 
mamma  etc.  In  consequence  of  this,  the  diseased  breast  sloughed  clean 
away,  leaving  a  healthy  granulating  surface,  which  rapidly  cicatrized. 
There  was  no  return  of  the  disease  in  this  locality  ;  -but,  the  undestroyed 
part  in  the  axilla  spread  rapidly,  and  the  patient  died  soon  afterwards, 
with  symptoms  of  internal  dissemination. 

Billroth  has  reported  an  instance  in  which  a  mammary  cancer  of 
seven  years'  duration,  and  the  size  of  an  apple,  exfoliated  spontaneously 
bv  dry  gangrene,  the  wound  cicatrizing  rapidly.  When  shown  at  the 
Berlin  Medical  Society  (1893)  shortly  afterwards,  the  cicatrix  was  quite 
sound,  but  its  edges  were  raised  and  hard. 

1  "American  System  of  Gynaecology,"  vol.  ii. 

St.  Bartholomew's  Hospital  Reports,  1887,  vol.  xxiii.,  p.  147. 
3  British  Medical  Journal,  1900,  vol.  ii.,  p.  1259 


INFLAMMATION,  ULCERATION,  RETROGRESSION        489 

Like  their  physiological  prototypes  of  the  mamma,  sebaceous  glands 
and  epidermis,  the  cells  of  breast  cancers  are  short-lived.  Hardly  ever 
can  one  examine  a  cancerous  tumour  without  discovering  some  of  its 
cells  in  fatly  degeneration,  and  this  eventually  ends  in  their  complete  dis- 
integration. Such  conditions  have  little  or  nothing  to  do  with  circulatory 
disturbances  ;  they  occur  as  regular  stages  in  the  evolution  of  the  disease, 
owing  to  molecular  changes  inherent  to  the  cells  themselves.  To  this 
cause  we  must  attribute  the  tendency  of  cancers  to  spontaneous  ulcera- 
tion,  at  a  certain  stage  of  their  development ;  which  may  begin,  as  Hunter 
pointed  out,  either  superficially  or  deeply.  In  the  former  circumstance,  the 
growing  tumour  becomes  adherent  to  the  overlying  skin,  which  gets 
thinned  and  excoriated,  and  eventually  yields,  leaving  the  surface  of  the 
neoplasm  exposed,  and  this  consequently  ulcerates  ;  in  the  latter,  the 
changes  leading  to  ulceration  begin  in  the  substance  of  the  neoplasm,  and 
open  outwards.  Ulceration  once  started,  usually  tends  to  spread  in- 
definitely ;  yet  a  cancerous  neoplasm  is  never  completely  destroyed  in 
this  way,  for  the  disease  progresses  faster  than  the  ulcerative  process. 
Many  cancers  never  ulcerate  ;  this  was  the  case  in  twelve  of  the  forty- 
three  fatal  mammary  cases  under  my  observation  :  ulceration  rarely 
supervenes  in  this  form  of  the  disease,  until  the  malady  is  fairly  advanced. 

The  typical  ulcer  of  cancer  presents  as  an  irregularly  rounded,  exca- 
vated, crater-like  cavity,  with  hard,  raised,  swollen,  craggy  edges,  which 
are  usually  everted  ;  and  to  these  edges  the  surrounding  skin  is  always 
adherent.  It  appears  as  if  scooped  out  of  the  subjacent  cancerous 
growth,  hence  its  hardness  ;  hence  also  its  extensive  union  with  adjacent 
structures. 

Cancerous  ulcers  of  long  standing,  often  present  quite  a  different  aspect 
to  the  foregoing  :  they  are  shallow,  with  slightly  raised  and  sinuous 
edges,  the  base  comparatively  smooth,  and  covered  with  small  granula- 
tions, which  in  places  have  a  florid  and  almost  healthy  appearance.  A 
thin  parchment-like  layer  of  indurated  cancerous  tissue  underlies  the 
whole  affected  area,  and  binds  it  to  the  subjacent  structures.  Such 
ulcers  not  infrequently  cicatrize  more  or  less  extensively  ;  they  may 
even  be  covered  over  by  scar  tissue,  and  remain  for  considerable  periods 
in  a  non-progressive,  quiescent  state.  These  favourable  changes  are 
closely  allied  to  those  which  determine  the  atrophic  form  of  the  disease  ; 
but  I  cannot  cite  a  single  case  of  definitive  cure  by  ulceration,  although 
hundreds  of  alleged  "  cures  "  of  this  kind  of  lesion  have  been  reported. 

Epithelioma  of  the  lower  lip,  has  a  special  proclivity  to  heal  over 
in  this  manner,  the  primary  disease  shrinking  in  size  so  as  to  be  hardly 
noticeable  ;  and  yet,  after  a  time,  secondary  growths  appear  in  the 
adjacent  lymph-glands.  Interesting  examples  of  this  have  been  reported 
by  Merkens,1  Hendry,2  Freeman  and  others. 

Similar  conditions  are  also  met  in  connexion  with  cutaneous  cancers, 
especially  in  connexion  with  the  penis,  scrotum,  vulva  etc.3 

Moreover,  it  must  be  borne  in  mind,  that  in  all  these  localities  quasi 

1  Deutsche  Zeitschr.  f.  Chir.,  November,  1902. 

2  New  Zealand  Medical  Journal,  March  31,  1903. 

3  For  further  reference  4o  cases  of  this  kind,  vide  Chapter  XIX.,  p.  426. 


490  THE  NATURAL  HISTORY  OF  CANCER 

malignant  chronic  ulcerative  lesions,  with  a  healing  tendency,  are  often 
met  with  of  tuberculous,  syphilitic,  or  other  non-malignant  causation. 

Some  interesting  examples  of  this  kind,  affecting  the  tip  of  the  nose, 
have  lately  been  described  by  Du  Castel  *  and  Crouch.2 

Various  forms  of  abnormal  fat  formation  in  malignant  tumours,  arise 
in  connexion  with  circulatory  disturbances,  influencing  the  metabolism 
of  their  cells.  Thus,  parts  where  growth  is  exceedingly  active,  sometimes 
exhibit  a  kind  of  local  embonpoint  ;  that  is  to  say,  fat  globules  are  separated 
and  deposited  in  them,  which  would  have  been  oxidized  and  removed, 
but  for  the  local  supply  of  nutritive  materials  being  in  excess  of  me- 
tabolism. 

Here  mention  may  be  made  of  the  fact  that  an  organ  containing  a 
cancerous  tumour,  such  as  the  breast,  sometimes  gets  surrounded  by 
abnormal  fatty  growth,  owing  to  circulatory  disturbances  of  this  kind 
(capsular  lipomatosis). 

Localized  fatty  degenerations,  due  to  deficient  blood  -  supply 
through  venous  congestion,  inflammation,  thrombosis,  arteritis  etc.,  are 
of  frequent  occurrence.  When  the  arteries  are  seriously  interfered  with, 
considerable  areas  of  the  neoplasm  may  thus  be  rendered  necrobiotic. 
In  such  cases,  not  only  the  cells,  but  the  stroma  also  may  degenerate — 
as  in  the  so-called  lipomatous  cancers. 

In  like  manner  arise  the  areas  of  caseous  softening,  sometimes  seen 
irregularly  scattered  throughout  cancerous  tumours,  as  in  the  so-called 
caseating  cancers.  The  ultimate  fate  of  such  lesions  is  chiefly  dependent 
upon  the  subsequent  cellular  changes  ;  if  these  go  on  to  complete  dis- 
integration, the  resulting  products  may  be  absorbed  and  completely 
disappear,  or  they  may  liquefy  and  form  cysts,  or  caseate  and  eventually 
even  cretify. 

V  A  healthy-looking,  childless,  married  woman,  aged  thirty-three, 
under  Bryant's  3  care,  had  an  ulcerated  cancerous  tumour  of  the  right 
breast,  of  stony  hardness,  and  firmly  fixed  to  the  pectoral  muscle.  The 
tumour  was  of  six  years'  duration,  and  it  had  been  ulcerated  for  four 
years.  The  ulcer  was  the  size  of  the  palm  of  the  hand — its  edges  being 
nodular  and  crumbly.  The  axillary  glands  were  enlarged  and  hard. 
Operative  interference  was  declined.  Fifteen  months  later,  the  tumour 
was  obviously  smaller  and  harder  ;  and  several  pieces — the  size  of  nuts — 
had  shed  from  its  edge.  Six  months  later  it  had  still  further  diminished, 
and  much  of  the  original  tumour  had  crumbled  away.  Some  discrete 
cancerous  tubercles  now  appeared,  in  the  adjacent  skin  over  the  sternum. 
In  the  course  of  the  next  year,  the  tumour  continued  to  contract  and  to 
throw  off  pieces.  The  cutaneous  tubercles  notably  diminished,  and  the 
axillary  glands  got  smaller  and  harder.  Two  years  later,  the  ulcer  had 
almost  completely  cicatrized — a  puckered  linear  scar  was  all  that  re- 
mained, in  which  were  a  few  small,  hard  nodules.  The  tubercles  in  the 
adjacent  skin  had  completely  disappeared.  A  year  later,  all  that  re- 

1  Medical  Press  and  Circular,  1901,  vol.  ii.,  p.  623. 

2  Bristol  Medico-Chirurgical  Journal,  September,  1903,  p.  23. 

3  "Diseases    of    the    Breast,"    1887,    p.    142;    for  other    cases    of   this    kind   vide 
bt.  Bartholomew's  Hospital  Reports,  1891,  vol.  xxvii.  (Masterman). 


INFLAMMATION,  ULCERATION,  RETROGRESSION       491 

mained  of  the  original  disease  was  a  single  nodule,  the  size  of  a  hazel-nut, 
in  the  scar.  The  axillary  glands  were  hardly  perceptible.  The  patient's 
general  health  was  unimpaired.  One  and  a  half  years  later,  she  again 
came  under  observation  ;  during  this  interval  several  fresh  tubercles  had 
appeared  in  the  skin,  near  the  cicatrix,  and  had  subsequently  disappeared, 
so  that  only  two  small  ones  now  remained.  The  patient  considered 
herself  quite  well.  She  died  five  and  a  half  years  later,  of  some  pul- 
monary complication,  without  any  obvious  increase  of  the  local  disease 
having  taken  place.  Altogether  the  disease  had  lasted  for  nearly 
nineteen  years. 

There  is  in  the  Hunterian  Museum,1  a  remarkable  specimen  of  atrophic    / 
epidermoidal  cancer  of  the  base  of  the  tongue,  in  which  nearly  the  whole 
organ  disappeared  during  the  course  of  the  disease,  the  disappearance 
being  unaccompanied  by  ulceration. 

Unfortunately,  even  with  these  retrogressing  forms  of  cancer,  the 
malady  continues  to  spread  at  the  growing  edge. 

The  so-called  "calcifying  epitheliomata "  of  the  skin  etc.,  which  may 
exfoliate,  and  are  sometimes  cited  as  examples  of  cancer  cured  by  calci- 
fication, are  essentially  non-malignant  formations  of  adenomatous 
nature. 

The  changes  produced  in  cancerous  tumours  by  colloid,  myxomatous, 
and  atrophic  metamorphoses,  constitute  special  well-recognized  varieties 
of  the  disease,  which  need  not  be  further  particularized  here. 

I  have  before  mentioned,  that  the  characteristic  feature  of  cancer  is 
its  tendency  to  persist  indefinitely,  and  to  increase  continuously.  Yet 
indications  are  not  wanting  of  occasional  spontaneous  retardation  and 
arrest  of  the  disease,  and  even  of  its  retrogression  ;  but  I  cannot  cite  a 
single  instance  of  its  complete  spontaneous  cure.  Nevertheless,  in  face 
of  the  following  facts,  I  think  it  would  be  rash  altogether  to  deny  the 
possibility  of  such  a  fortunate  occurrence. 

The  extreme  chronicity  of  certain  cases  of  cancer  shows,  that  the 
increase  of  the  disease  may  sometimes  b3  so  exceedingly  slow,  as  hardly 
to  be  appreciable.  Instances  of  this  kind  are  of  more  frequent  occur- 
rence in  the  breast  than  is  generally  believed  ;  and,  what  is  still  less 
appreciated  is,  that  the  great  majority  of  such  cases  are  morphologically 
indistinguishable  from  ordinary  acinous  cancer  (scirrhus),  being  neither 
of  the  atrophic  nor  of  the  colloid  variety,  although  both  atrophic  and 
colloid  cancers  exhibit,  in  a  high  degree,  the  tendency  to  chronicity  and 
retardation. 

Instances  of  this  kind  may  be  met  with  in  the  malignant  tumours  of 
all  parts  of  the  body. 

The  following  are  some  of  the  best  examples  of  these  retrogressing 
cancers  known  to  me  : — 

A  young  woman  consulted  Osier,2  for  a  lump  in  her  breast  of  more 
than  four  years'  duration.  The  part  was  removed  shortly  afterwards, 
together  with  the  tumour,  which  was  "  undoubtedly  cancerous  in  nature." 
Two  years  later  she  was  seen,  with  symptoms  of  choroidal  metastasis  ; 
and,  some  months  later,  recurrent  nodules  appeared  in  the  other 
1  No.  2,273,  Pathological  Series.  2  Canadian  Practitioner,  1901. 


492  THE  NATURAL  HISTORY  OF  CANCER 

breast,  with  loss  of  power  of  the  legs,  and  indications  of  dissemination 
in  the  liver.  Morphine  was  prescribed,  but  nothing  else  was  done.  Some 
time  later,  when  Osier  saw  her  again,  he  was  surprised  to  find  that  the 
secondary  nodules  in  the  breast  had  disappeared,  she  had  regained  the 
power  of  walking,  and  the  vision  of  the  affected  eye  had  much  im- 
proved. 

In  another  case  by  the  same  doctor,  after  the  removal  of  a  cancerous 
tumour  from  the  breast,  the  patient  developed  "  girdle  pains  "  and  pain 
in  the  legs,  with  paraplegia.  Great  weakness  supervened,  and  she 
appeared  to  be  moribund.  Then  gradual  improvement  set  in  spon- 
taneously ;  many  of  the  recurrent  nodules  disappeared  ;  as  also  did  the 
pains  and  paraplegia.  She  was  able  to  get  up  and  walk  about,  although 
she  still  had  "  a  stiff  back." 

It  would  be  interesting  to  know  the  final  results  in  these  cases. 

In  a  case  lately  described  by  MacKay.1  the  patient  was  a  spinster, 
aged  thirty-seven,  with  cancer  of  the  breast,  which  retrogressed  in  the 
penultimate  stage  ;  when  the  patient  was  in  a  hopeless,  collapsed,  and 
"  half-starving  condition,"  with  double  hydrothorax  etc. 
X  Gould  2  has  reported  two  somewhat  similar  instances. 

In  the  first  of  these,  the  patient,  aged  forty-one,  had  her  left  breast 
removed,  together  with  the  axillary  glands,  for  cancer  of  over  a  year's 
duration.  Five  months  later,  symptoms  of  double  pyosalpinx  having 
appeared,  both  ovaries  and  tubes  were  removed  by  laparotomy.  Two 
and  a  half  years  later  she  was  seen  again,  when  there  were  recurrent 
nodules  in  the  mammary  region  and  axilla,  as  well  as  in  the  supra- 
clavicular  region.  The  liver  was  large  and  nodular,  and  there  was 
hydroperitoneum,  as  well  as  a  discharging  sinus  in  the  laparotomy 
scar.  She  was  in  a  very  feeble  and  emaciated  condition.  No  further 
operative  or  other  special  treatment  was  adopted.  In  the  course  of  the 
next  few  years,  the  recurrent  nodules  of  the  chest-wall  disappeared, 
except  a  single  small  one  near  the  scar  ;  the  enlarged  axillary  and  supra- 
clavicular  glands  also  dispersed  ;  the  liver  became  much  smaller  and  the 
hydroperitoneum  diminished.  Meanwhile  her  general  health  so  much 
improved,  that  she  got  up  and  left  the  hospital. 

In  another  case,  the  patient  was  a  single  woman,  aged  forty-seven, 
whose  left  breast  had  been  amputated  nine  years  before,  for  a  tumour 
of  two  years'  duration,  which  on  microscopical  examination  after  re- 
moval, was  found  to  be  "  typical  scirrhous  cancer."  Two  years  after 
this  operation,  there  was  recurrence  in  the  left  axilla,  which  was  removed. 
Two  years  later  there  was  recurrence  in  the  left  chest,  and  above  the 
right  mamma.  About  this  time  the  menopause  supervened.  The 
recurrent  disease  was  now  again  extirpated  ;  but,  soon  afterwards,  fresh 
recurrent  nodules  formed  in  both  mammary  regions,  in  the  axillse,  and 
in  the  lower  part  of  the  neck  on  each  side.  She  suffered  from  shortness 
of  breath,  orthopnoea  and  symptoms  of  invasion  in  the  right  lung  and 
pleura.  About  this  time  a  lump  appeared  at  the  upper  part  of  the  right 

1  British  Medical  Journal,  1907,  vol.  ii.,  p.  138. 

2  Clinical    Society's   Transactions,  London,    1897,  vol.  xxx.,  p.    205  ;    also  Clinical 
Journal,  1902,  vol.  xx.,  pp.  96  and  120. 


INFLAMMATION,  ULCERATION,  RETROGRESSION        493 

femur,  which  underwent  spontaneous  fracture.  Her  general  condition 
was  now  such,  that  she  was  considered  to  be  in  articulo  mortis.  No 
special  treatment  of  any  kind  was  adopted.  Strange  to  relate,  in  the 
course  of  a  few  months,  her  condition  greatly  improved  ;  she  lost  the 
orthopnoea,  and  most  of  the  recurrent  nodules  disappeared.  The  femoral 
tumour  vanished,  and  the  fractured  bone  consolidated.  In  this  improved 
condition,  she  has  remained  for  several  years. 

In  a  case  by  J.  Hutchinson,1  the  whole  of  the  right  mammary  region 
was  occupied  by  a  thin,  smooth,  parchment-like,  glossy  scar,  which 
extended  backwards  beyond  the  mid-axillary  line  ;  its  edge  being  slightly 
elevated,  hard  and  sinuous,  like  that  of  rodent  ulcer.  Near  this  large, 
scar-like  area,  were  several  small,  isolated  patches  of  similar  appearance. 
The  left  mammary  region  was  affected  in  the  same  way.  Near  the 
anterior  border  of  the  left  axilla  was  a  subcutaneous  nodule,  the  size  of 
a  hazel-nut.  This  was  the  only  situation  in  which  the  growth  had  any 
thickness.  Nowhere  was  there  even  a  trace  of  ulceration.  There  were 
a  few  hard  glands  in  each  axilla,  none  of  them  larger  than  horse- 
beans. 

The  disease  began  as  a  hard  tumour  in  the  right  breast,  thirteen 
years  previously,  and  it  only  subsequently  invaded  the  left  breast. 
Never  at  any  stage  had  it  ulcerated.  The  patient  consulted  Hutchinson 
on  account  of  pulmonary  complication  of  recent  development,  which 
was  thought  to  be  due  to  fluid  in  the  right  pleura.  After  the  chest  had 
been  tapped  several  times,  without  any  fluid  being  discovered,  it  became 
evident  that  the  dulness  was  due  to  intra-thoracic  solid  growth.  The 
patient  died  about  two  months  later  from  this  cause  ;  but  there  was  no 
necropsy. 

The  two  following  cases,  by  Broca,2  are  also  of  much  interest  : 

1.  A  woman,  aged  sixty-nine,  who  died  in  hospital  with  secondary 
cancer  of  the  liver.  She  was  admitted  with  extensive  chronic  ulceration  of 
the  mammary  region,  which  had  supervened  on  hard  cancer  of  the  breast 
of  many  years'  duration.     The  ulcer  was  shallow  ;  its  edges  but  slightly 
raised  ;  and  it  had  commenced  to  cicatrize  in  several  places.     On  micro- 
scopical examination  of  the  part  after  death,   it  was  found  that  the 
whole  of  the  cancerous  growth  had  been  destroyed  by  ulceration,  except 
a  single  nodule — the  size  of  a  hazel-nut — near  the  centre  of  the  ulcer. 

2.  A  lady,  who  when  first  seen  had  an  irregular  scar  in  the  mammary 
region,   in  connexion  with  which  there  was  a  small,   hard,   cancerous 
nodule  of  some  months'  growth.     She  said  that,  fifteen  years  previously, 
she  first  noticed  a  tumour  in  her  breast,  which  subsequently  ulcerated  ; 
and,  after  a  time,  healed  up  without  any  operation  ever  having  been 
done.     Some  time  afterwards,  however,  a  fresh  growth  appeared  in  the 
cicatrix,  which  later  on  ulcerated  ;  but,  again  the  ulcer  healed  spon- 
taneously, after  which  the  present  recurrence  set  in.     She  refused  oper- 
ative treatment.     The  disease  subsequently  progressed  so  rapidly,  that 
she  died  of  it  a  few  months  later. 

Some  instances  of  retrogression,  as  in  the  two  following  cases  by 

1   Archives  of  Surgery,  April,  1891,  vol.  ii.,  No.  8,  p.  354. 
a  "  Traite  dea  Tumeurs,"  1866.  t.  i.,  p.  240. 


494  THE  NATURAL  HISTORY  OF  CANCER 

Billroth  l  and  Walshe,2  coincide  with  its  outbreak  in  remote  parts  of  the 
body.  These  seem  greatly  to  have  impressed  the  old  surgeons,  who 
erroneously  regarded  them  as  true  metastases,  which  term  they  hence- 
forth applied  to  all  systemic  disseminations. 

1.  A  woman,  aged  forty,  with  an  infiltrating  cancerous  tumour  of  the 
left  breast,  the  size  of  an  apple,  who  refused  operation.     One  year  later, 
she  again  came  under  treatment  with  paraplegia,  due  to  dissemination  of 
the  disease  in  the  vertebrae.     The  former  tumour,  with  its  surrounding 
infiltration,  had  completely  disappeared  ;  in  its  place  nothing  remained 
but  a  flat,  indurated,  superficial  scar,  which  was  slightly  excoriated. 

2.  A  very  cachectic  woman,  with  non-ulcerated,  hard  cancer  of  the 
breast,  of  two  years'  duration,  was  seized  with  violent  cephalalagia,  fol- 
lowed by  apoplectic  symptoms  with  hemiplegia.     At  about  the  time  of 
this  attack,  the  mammary  tumour  notably  diminished  ;  and,  when  she 
died,    ten   weeks   later,    it   had    almost   completely   disappeared.     The 
necropsy  revealed  a  cancerous  tumour,  the  size  of  a  nut,  in  the  brain. 

In  the  next  case,  by  Paget,3  subsidence  of  the  cancerous  disease, 
coincided  with  the  active  progress  of  pulmonary  tubercle. 

The  patient  was  only  twenty-five  years  old,  yet  she  had  a  large, 
hard,  cancerous  tumour  of  the  breast.  The  disease  had  progressed  very 
rapidly,  its  total  duration  being  only  three  months.  The  overlying  skin 
and  nipple  were  invaded.  The  axillary  glands  were  enlarged  and  hard. 
The  breast  was  amputated  ;  after  which  the  swelling  of  the  axillary  glands 
subsided.  Six  months  later,  there  was  recurrence  in  the  mammary 
region  and  in  the  axilla.  In  the  former  situation,  the  disease  made 
rapid  progress  ;  numerous  tubercles  formed  in  its  vicinity,  which  coalesced, 
and  eventually  ulcerated.  Thus  it  progressed  for  a  year,  when  the 
ulcer  began  to  cicatrize  ;  and,  in  the  course  of  six  months,  it  had  almost 
completely  healed.  The  axillary  disease  also  subsided,  one  hard 
lump  alone  remaining  of  what  had  been  a  large  cluster  of  hard  glands. 
Meanwhile,  however,  the  patient  had  emaciated  and  lost  strength  ;  and 
she  died,  about  two  years  after  the  operation,  and  six  months  after  the 
cancer  had  so  nearly  healed,  of  tuberculosis  of  both  lungs.  On  careful 
examination  of  the  mammary  region  after  death,  a  thin,  flattened,  nodular 
plaque  of  extremely  hard  and  dense  cancer,  was  found  beneath  the  old 
scar,  binding  it  to  the  pectoral  muscle.  In  the  axilla  was  a  single  hard 
cancerous  gland  ;  and  the  liver  contained  several  equally  hard  growths. 

Sigg  4  and  others  have  met  with  similar  cases. 

Perrion  5  has  seen  mammary  cancer  subside,  after  an  operation  for 
goitre  followed  by  much  suppuration  ;  and  Jahr 6  has  reported  the 
retrogression  of  mammary  sarcoma,  after  artificially  induced  delivery. 

Several  instances  of  these  "  retrogressing  cancers  "  have  been  met 
with  in  connexion  with  the  uterus,  among  others  by  Sanger,  Rokitansky, 
Klob  and  Scanzoni ;  but,  no  well-substantiated  example  of  spontaneous 

1  Deutsche  Chir.,  1880,  Lief,  xli.,  S.  106. 

"  Nature  and  Treatment  of  Cancer,"  1846,  p.  110. 

"Lectures  on  Surgical  Pathology,"  1853,  vol.  ii.,  p.  337. 
4  Corresp.-blatt.  f.  schweizer  Aerzte,  April  15,  1891. 
6  Bev.  Med.  de  la  Suisse  Rbmande,  t.  xi.,  p.  195. 
6  Berlin,  klin.  Woch.,  July  30,  1894,  S.  726. 


INFLAMMATION,  ULCERATION,  RETROGRESSION        495 

cure  is  known  to  me,  although  in  some  cases  of  "  corroding  ulcer  " 
(epithelioma  uteri  superficiale)  the  anatomical  evidence  of  the  disease  was 
very  slight,  as  in  the  following  case  under  my  observation  : 

A  single  woman,  aged  sixty-one,  who  had  never  been  pregnant, 
having  suffered  for  nearly  four  years  from  symptoms  of  uterine  cancer, 
died  of  asthenia,  no  operation  having  been  done.  At  the  necropsv,  the 
body  was  found  to  be  extremely  emaciated.  The  whole  of  the  uterus  had 
disappeared,  with  the  exception  of  its  thickened  peritoneal  covering, 
which  circumscribed  a  pouch,  the  size  of  a  small  orange,  into  which 
the  vagina  led  directly.  The  interior  of  this  cavity  and  the  upper  part 
of  the  vagina,  presented  a  softish,  granular,  yellowish-green,  smooth 
discharging  surface,  in  connexion  with  which  no  induration  or  infiltration 
was  apparent.  The  adjacent  parts  seemed  equally  free  from  cancerous 
disease.  Into  the  front  of  this  cavity  the  bladder  opened,  and  into  its 
back  the  rectum,  each  by  a  rounded  opening,  the  size  of  a  florin.  The 
atrophied  ovaries  were  adherent  to  the  outside  of  the  peritoneal  pouch 
representing  the  uterus.  This  pouch  was  further  strengthened  by  the 
matting  together  of  the  adjacent  pelvic  structures,  so  that  no  perforation 
into  the  peritoneal  sac  had  occurred.  There  was  slight  double  hydro- 
nephrosis.  No  infiltrated  glands  could  be  discovered,  nor  were  there 
any  secondary  cancerous  deposits  elsewhere.  The  other  organs  were 
normal.  Microscopical  examination  of  the  wall  of  the  eroded  cavity, 
revealed  scanty  fibrillar  tissue,  densely  infiltrated  with  small  round 
cells  (lymphocytes).  Embedded  here  and  there  in  this  structure,  were 
lobular  epithelial  masses,  consisting  of  solid  aggregations  of  small, 
irregularly  shaped,  epithelial  cells,  presenting  no  signs  of  epidermic 
evolution,  and  no  "  nests."  Many  of  the  cells  were  in  advanced  stages 
of  granular  degeneration.  These  structures  did  not  penetrate  deeply. 
Beneath  them  was  a  thin  layer  of  the  fibro-myomatous  tissue  of  the 
uterine  wall,  infiltrated  with  small  round  cells. 

Rokitansky's  case  [  of  alleged  cure  by  sloughing  and  ulceration,  with 
the  subsequent  formation  of  a  funnel-shaped  scar,  is  by  no  means 
convincing. 

Teallier  2  has  witnessed  marked  retardation  of  uterine  cancer  during 
lactation  ;  while,  by  Blanchard  3  and  Fleury,4  remarkable  examples  of 
the  arrest  and  retardation  of  the  disease  have  been  reported,  in  patients 
reduced  to  the  last  extremity  of  debility  by  the  malady. 

In  cases  of  intra-abdominal  malignant  disease,  Bidwell,5  B.  Clarke,6 
H.  Snow  7  and  others,  have  observed  marked  amelioration,  after  simple 
exploratory  laparotomy.  Beatson's  cases  of  regression  of  mammary 
cancer  after  oophorectomy,  probably  belong  to  this  category.  Malignant 
tumours  have  also  been  known  to  retrogress  after  partial  removal,  as  in 
cases  reported  by  Riqhardson,8  Munro  Smith 9  and  others.  Similar 

"  Pathological  Anatomy  "  (English  translation),  3rd  edit.,  vol.  iii.,  p.  495. 

"  Du  Cancer  de  la  Matrice."  Paris,  1836,  p.  227. 

Marseille  Med.,  1869,  t.  vi.,  S.  997. 

Arch.  Med.  Beiges,  Bruxelles,  1863,  t.  xxxii.,  p.  98. 

Lancet,  1897,  vol.  ii.,  p.  1346.  6  Clinical  Journal,  February  6,  1907,  p.  264. 

British  Medical  Journal,  1897,  vol.  i.,  p.  1414. 

8  Annals  of  Surgery,  December,  1898,  p.  741. 

9  Bristol  Medico- Chirurgical  Journal,  March,  1900. 


496  THE  NATURAL  HISTORY  OF  CANCER 

results  have  ensued  after  thyroid  medication,  tuberculin  injections, 
injections  with  the  toxins  of  erysipelas,  and  in  the  various  phases  of 
serum-therapy. 

Many  interesting  particulars  relating  to  cases  of  this  kind,  will  be 
found  in  the  publications  of  H.  Mohr  1  and  Lomer.2 

Reviewing  these  various  typical  examples  of  arrest  and  retardation 
of  the  disease,  it  appears  that  they  may  be  grouped  under  the  following 
headings  : 

1.  In  the  penultimate  stage  of  the  cancerous  cachexia,  and  in  most 
illnesses  causing  great  wasting  and  exhaustion  (e.g.,  phthisis),  cancerous 
growths  may  become  stationary  and  retrogressive. 

2.  Acute  infective  diseases  may  exert  a  similar  retarding  influence  on 
the   growth    of   malignant    tumours,    as   is   especially   noticeable   with 
erysipelas.      Such  remission  of  the  disease  as  is  noticeable  after  injec- 
tions of  the  toxins  of  erysipelas,  and  Coley's  fluid,  may  also  be  cited,  in 
this  connexion. 

3.  In  another  class  of  cases,  similar  results  have  followed  various 
operative    procedures,    such    as    laparotomy,    partial    removal    of    the 
malignant  tumour  etc.     To  this  category,  Beatson's  cases  of  retrogres- 
sion of  mammary  cancer  after  oophorectomy,  probably  belong ;  and  also 
the  X-ray  treatment,  which  seems  to  be  effective  as  well  through  the 
local  inflammatory  action  excited,  as  through  concomitant  changes  in  the 
blood,  and  the  system  in  general,  especially  the  sexual  system.     In  this 
connexion  it  may  be  remembered,  that  it  was  formerly  the  custom  to 
prevent  wounds  made  for  the  removal  of  cancer,  he,aling  by  first  inten- 
tion, under  the  impression  that  recurrence  was  thereby  retarded. 

4.  Retrogression  of  the  local  disease,  may  coincide  with  the  outbreak  of 
fresh  foci  in  remote  parts  of  the  body,  as  if  there  had  been  real  metastasis. 

5.  In  a  considerable  number  of  instances  the  growth  of  malignant 
tumours  is  arrested,  without  there  being  any  obvious   concomitant  to 
account  for  it,  other  than  extreme  general  debility. 

It  is  quite  evident,  when  we  bear  in  mind  the  many  various  con- 
ditions with  which  the  retrogression  of  malignant  tumours  is  associated, 
that  there  can  be  nothing  specific  about  it.  Indeed,  the  only  feature 
common  to  all  such  cases,  is  the  extremely  debilitated  condition  to  which 
the  patients  are  reduced  ;  and,  I  think  there  can  be  no  doubt,  that 
enfeebled  vitality  is  the  chief  cause  of  such  improvement  as  is  noticeable. 
As  Luschi  and  others  have  shown,  in  conditions  of  this  kind,  the  glycogen 
and  carbohydrates  of  the  body  are  used  up  and  attenuated,  to  such  an 
extent,  as  to  render  active  cell  proliferation  almost  impossible.  Such 
patients  are,  in  fact,  reduced  to  a  state  similar  to  that  brought  about  by 
the  starvation-treatment  of  cancer,  as  formerly  practised  with  some 
success  by  Huf eland  and  others. 

1  Therapeutische  Monatschr.,  1903,  Heft  11  and  12. 

2  Zeitschr.  f.  Geb.  u.  Gyn.,  Bd.  1.,  Heft  2. 


BILLING   AND   SONS,    LIMITED,    PRINTERS,    GUILDKORD 


INDEX   OF   SUBJECTS 


ABDOMINAL  quasi-malignant  disappearing 

tumours,  486,  495 
Aborigines,  rarity  of  cancer  in,  21,  40,  41, 

43,  44,  45,  46,  48,  78 

Abortion  and  congenital  deformities,   in- 
crease of,  24,  50,  88 
Aaurihosis  nigricans  and  in tra -abdominal 

cancer,  347 

Acute  cancer,  448,  452 
Adenopathy    (supra-clavicular),    Troisier's 

symptom,  424  ;  inguinal,  426 
Adrenal  disease  and  cancer,  215,  216,  310 
^Etiological   indications,    3,   4,    12-24,    25, 

26,  28,  30,  40,  41,  46,  58,  59,  61,  120,  133, 

139,  214,  330,  332  (Chap.  XVI.) 
Africa,   rarity  of   cancer   in,   22  ;   general 

survey  of  its  distribution  in,  42 
Agamogenesis,   3,   26,    119,   134-139,  207, 

212,  213,  214 
Ago  incidence  of  cancer  in  animals,  90  ; 

in  humanity,  317  (Chap.  XV.) ;  maximum 

Sroclivity,  318 ;  cancer  not  a  senile 
isoase,  320  ;  centenarians  and  cancer, 
319  ;  congenital  and  early  life  cases,  90, 
323,  325  ;  statistics  of,  317  ;  in  relation 
to  localization,  321,  and  sex,  316  ;  in 
relation  to  growth,  development,  and  re- 
production, 330  ;  senescence,  203 

Albumin  of  cancer,  214,  219,  407,  408  ; 
albumosuria  and  albuminuria  in  the 
cancerous,  477 

Alcohol  and  cancer,  67,  351 

Algeria,  rarity  of  cancer  among  the 
aborigines,  43 

Alimentation  and  cancer  proclivity,  12,  14, 
23,  25,  26,  28,  31,  35,  43,  46,  59,  61,  64, 
65,  66,  67,  68,  91,  94  (monkeys),  212, 
214,  332,  333,  345,  347,  349,  353  ;  vide 
also  Meat  consumption 

Alternation  of  generations,  138,  207 

America,  distribution  of  cancer  in,  22 ; 
British  North,  22,  47  ;  United  States,  22  ; 
46,  47,  76  ;  Central,  22,  47  ;  South,  22,  48 

Amphibians,  cancer  and  tumours  of,  112 

Amyloid  changes,  rarity  of,  in  cancer,  477 

Anabolism,  cancer  the  outcome  of  pre- 
dominant, 26 

Animals,  cancer  and  tumours  of,  87 
(Chap.  V.)  ;  rarity  of  cancer  in  wild,  87, 
88  ;  cancer  of  wild  animals  in  captivity, 
88,  91,  92,  107,  110,  112,  113,  114 

Antiquity  of  cancer,  50 

Apoplexy,  undue  prevalence  among  the 
relatives  of  the  cancerous,  372 

Arctic  regions,  cancer  in,  20,  21 


Argentina,  cancer  incidence,  49 

Arthritism  and  cancer,  335,  373 

Asia,  cancer  proclivity  of,  22,  30 

Ass,  cases  of  sarcoma,  103 

Association  of  epithelioma  and  sarcoma, 
300,  301,  303,  304  ;  of  cancer  with  non- 
malignant  tumours,  310 

Asthenia  as  the  mode  of  death  in  cancer, 
478 

Atavism  in  cancer,  368  ;  in  the  royal 
family,  369 

Atrophic  varieties  of  cancer,  450,  489,  490, 
491,  492,  493 

Atypical  epithelial  proliferation,  5,  132, 
137,  173,  179,  187,  190,  485 

Australasia,  cancer  incidence  of,  22,  40  ; 
Australia,  41,  77  ;  New  Zealand,  41,  78  ; 
the  undue  proclivity  of  immigrants  to 
cancer,  41,  78 ;  immunity  of  the 
aborigines,  40,  78  ;  increase  of,  78 

Austria,  cancer  in,  25,  75 

Auto-inoculation  of  cancer,  197,  436;  of 
warts,  177 

BACTERIA    as    cancer   parasites,    233 ;    as 

epiphytes,  235 
Bath,   its   high   cancer  and   low   tubercle 

mortality,  59,  268,  269 
Bears,  cancer  of,  110 
Berlin,  cancer  death-rates,  27,  74 
•   Berwick  (county),  its  very  high  cancer  and 

low  tubercle  mortality,  69 
I   Betel-chewing  and  cancer  of  the  mouth,  37, 

38,  39 
!   Biological  theory  of  cancer,  the  author's, 

2,  3,  12,  13,  62,  87,  119,  132  ct  scq.,  201 

(Chap.  IX.) 

Birds,  tumours  of,  91,  111 
Birth-rate  and  cancer  proclivity,  353 
Bladder,     dissemination     of     cancer     in, 

438 

Blastema  theory  of  cancer,  131 
Blastogenic  tumour  germs,  139,  140,  141 
Blastomycetes    as    cancer    parasites,    249, 

261  ;   quasi-malignant   tumours  due  to, 

179,  181,  183,  190,  250,  252,  260,  427, 

484,  485 
riondes  and  cancer  proclivity,  20,  21 

lood    changes    in    cancer,    469    el    scq.  ; 

bloodvessels   of,   407  ;    cancer   cells   in 

the  blood,  411,  442,  444,  445,  446,  470  ; 

microbic  parasites  in,  235,  236,  247,  252, 

261  ;   blood   pressure   in   the   cancerous, 

333 ;    mtra-vascular    cancer,    430,    443, 

444,  445 


497 


498 


INDEX  OF  SUBJECTS 


Boers  and  European*  in  South  Africa,  their 
much  greater  proclivity  to  cancer  than 
tlio  natives,  46 

Bones,  dissemination  of  cancer  in,  427- 
438,  441  ;  Recklinghausen's  researches, 
446  ;  sarcoma  of,  91  (animals),  418,  438, 
439  ;  hetero topic  bone  formation,  148, 
149,  167  ;  primary  epithelioma  of  bone, 
409 

Brazil,  distribution  of  cancer  in,  49 
Breast  cancer,  increase  of,  in  England,  55, 
56  ;  in  United  States,  56  ;  in  animals,  89, 
90,  95  ;  genesis  of,  165-168  ;  precancerous 
conditions  (mastitis,  trauma  etc.),  274, 
286,  410  ;  Paget's  disease,  282  ;  adenoma 
and  cancer,  294  ;  bilateral  forms,  299, 
448  ;  initial  multiplicity,  304,  305,  306  ; 
mixed  forms,  308  ;  in  association  with 
non-malignant  tumours,  311  ;  superven- 
tion of,  after  ovariotomy,  464  ;  sex  inci- 
dence, 315,  380 ;  early-life  cases,  329  ; 
at  advanced  ages,  330  ;  family  history, 
358-360,  364,  365,  367-370;  hereditary 
proclivities  correlated  with,  370-374  ; 
tubercle  and  cancer,  337,  371  ;  relative 
frequency,  379-382  ;  proclivity  of  certain 
regions,  383  ;  statistical  tables,  394-399  ; 
the  primary  tumour,  402  ;  casein  in,  156  ; 
physiological  characters  of  cancer  of, 
403,  414  ;  likeness  of  primary  tumour 
to  prototype,  230;  chemical  analysis, 
407  ;  vascular  supply,  407  ;  nerves, 
407 ;  relation  to  lymphatics,  406 ; 
reaction  of,  408 ;  glycogen  of,  408 ; 
enzymes,  408 ;  heterotopic  forms,  in 
axilla  etc.,  409 ;  local  dissemination, 
410 ;  lymph  glandular  dissemination, 
412  ;  general  dissemination,  431  ;  meta- 
stases  in  cancer  of  male  breast,  432  ; 
dissemination  of  sarcoma,  416,  438 ; 
varieties  of  acute,  448,  449  ;  chronic, 
449-451  ;  recurrence  of,  454,  456,  457, 
458 ;  tardy  recurrence,  459,  460 ;  ca- 
chexia,  470 ;  diagnostic  fallacies,  480- 
483  ;  inflammation  and  suppuration  of, 
448,  487,  488  ;  sphacelus  of,  468  ;  ulcera- 
tion,  489  ;  fatty  and  caseating  forms, 
490 ;  capsular  lipomatosis  of,  490  ; 
retrogressing  forms,  490-494  ;  in  clogs, 
89,  90,  95  ;  in  cats,  98  ;  in  horses,  101  ; 
sarcoma  of,  167  ;  melanoma,  168 
Breast,  diseases  of,  references  to  the 
author's  book  on,  165,  166,  167,  295, 
305,  308,  317,  329,  349,  383,  401,  416, 
429,  431,  432,  448,  467,  476 
Broussaisian  theory  of  cancer,  119,  130, 

270,273 

Broussins  (tree  cancers,  burrs),  123-125 
Bud  formation  in  relation  to  tumours,  20, 
115-126,  118,  119,  134,  138,  139,  207,  208 

CACHEXIA,  7,  468  (Chap.  XXI.) 

Canada,  cancer  incidence,  47  ;  rarity  of 
among  the  aborigines,  47 

Cancer  mortality,  24  (Europe),  27,  28 
(towns),  30  (Asia),  33  (India).  40  (Aus- 
tralasia), 42  (Africa),  46  (America),  51, 
79  (England  and  Wales),  67  (Scotland), 


69  (Ireland),  70  (Switzerland),  71  (Den- 
mark), 72  (France),  73  (Sweden  and 
Norway),  74  (Holland  and  Germany), 
75  (Austria,  Hungary,  and  Italy),  76 
(United  States),  77"  (Australia),  78  (New 
Zealand)  ;  vide  Increase  of  cancer 

Cancer  and  tumour  formation,  principles 
of,  references  to  author's  book  on,  12,  13, 
87,  123,  132,  134,  135,  317 ;  definition  of 
the  term  "  cancer,"  10  ;  cancer  type,  66, 
332  ;  affinities  of  the  cancer  process,  3, 
12,  13,  131,  132,  134,  214  ;  essentially 
disintegrative,  213 

Capital  cities,  cancer  proclivity  of,  26,  27 
(European)  ;  41  (Australia),  47,  70  (New 
York)  ;  London,  27,  60,  82-86 

Captive  wild  animals,  cancer  of,  24,  87,  88, 
110 

Carcinoma,  definition  of  the  term,  10 

Cardiac  changes  in  the  cancerous,  340  ;  car- 
diac disease  in  cancer  families,  335 

Carnivora,  cancer  proclivity  of,  91,  92 

Carp,  tumours  of,  113 

Castration  and  cancer,  91,  100,  215,  404, 
465 

Cat,  tumours  of,  98,  99 

Celibacy,  late  marriages  etc.,  and  cancer, 
353 

Cell  theory  of  tumours,  130-133  ;  cancer 
cells,  4,  8,  400-406  ;  vide  also  Nucleus, 
Mitosis,  Chromosomes,  Polar  bodies, 
Endocytes 

Centenarians,  comparative  immunity  of 
from  cancer,  319,  320,  329,  330 

Centrosomes  of  cancer  cells,  218,  219 

Ceylon,  cancer  in,  39 

Chemistry  of  cancer,  6.  8,  9,  13,  126,  127, 
173,  214,  215,  216,  219,  220,  403,  407-409 

China,  cancer  in,  22,  30,  31  ;  Chinese  in 
United  States,  32  ;  in  Australia,  78 

Chondroma,  heterotopic,  of  uterus,  148, 
149 ;  chondrifying  myoma,  149,  sar- 
coma, 149,  154,  155,  epithelioma,  148; 
of  mamma,  167 

Chorio-epithelioma,  6,  324,  418,  420,  440, 
443,  446 

Choroid,  sarcoma  of,  419,  427,  429,  439, 
461,  467  ;  metastatic  cancer  of,  429,  432  ; 
heredity  of,  361  ;  in  twins,  362 

Chromosomes,  reduction  of,  211,  217,  405 
(heterotypical  mitosis) 

Chronic  inflammation  and  cancer,  5,  ll'J. 
130,  132,  133,  137,  173,  174,  181,  187, 
270,  273 

Chronic  varieties  of  cancer  449-453 

Civilization,  modern,  and  cancer  proclivity, 
13,  21,  58,  59,  62-67,  70 

Classification  of  tumours,  4,  10,  141 
(blastogenic  and  somatogenic) 

Clifton,  high  cancer  and  low  tubercle  mor- 
tality of,  59,  61 

Climate  and  cancer  proclivity,  22,  23,  24 

Cohnheim's  theory,  133,  139,  140,  142, 
143,  144 

Colloid  cancer,  450,  451 

Colon,  dissemination  of  cancer  of,  430,  437 

Comparison,  the  great  organon  of  patho- 
logy, 2 


INDEX  OF  SUBJECTS 


499 


Complexion  and  cancer  proclivity,  14,  20 

Concomitants  of  the  increasing  cancer 
•  mortality,  50 

Conditions  of  existence  in  relation  to  can- 
cer, 12,  14,  16,  17,  21,  25,  30,  42,  58,  62, 
65-67,  85,  135 

Condyloma,  a  disease  sui  generis,  con- 
tagiousness of,  178  ;  of  dogs,  97,  179, 
189 ;  ovarian  condyloma,  178,  296  ; 
grafting  experiments  with,  177 

Congenital  cancer,  90,  325  et  seq.  ;  con- 
genital defects  and  cancer,  50,  88,  139, 
144,  160,  165 

Conjugation  of  tissue  cells  as  cause  of 
cancer  genesis,  218,  405 

Consanguinity  and  cancer,  370 

Contagion  of  cancer,  the  question  of,  194- 
197,  262-269;  auto-iuoculability,  197- 
200,  436 

Convent  inmates  and  cancer  proclivity,  347 

Convicts  and  cancer,  345,  346 

Cuirassed  cancer  of  the  breast,  449 

Cure  of  cancer,  the  question  of,  488-496 

Cyst  formation  heterotopic  in  the  uterus, 
150,  151,  152  (dermoids),  153  ;  site  inci- 
dence of,  390,  394-399 

DEATH-RATE,  decline  of  the  general,  con- 
comitantly  with  increase  of  cancer 
mortality,  50,  66,  68,  69,  71,  73,  77,  78 

Deer,  rarity  of  cancer  in,  107 

Deformities,  congenital,  increase  of,  24,  50, 
88,  139-144,  160-168 

Denmark,  cancer  proclivity  of,  24,  71 

Density  of  population  in  relation  to  cancer 
proclivity,  30,  60,  61,  66,  85,  86,  354 

Dermatoses  of  the  cancerous,  347 

Dermoids  of  uterus,  151  ;  of  mamma,  167  ; 
of  bone,  epithelioma  of,  409  ;  experi- 
mental, 170  ;  traumatic,  171  ;  in  animals, 
97,  103,  105,  107,  112 

Developmental  irregularity  and  cancer, 
24,  139,  144,  160,  165,  325,  409 

Diabetes  and  cancer,  259,  334 ;  sugar- 
forming  substances  in  the  blood,  473  ;  in 
cancerous  tumours,  408 ;  proclivity  of 
Jews  to  diabetes,  16 

Diagnosis  of  cancer,  its  difficulties,  54, 
479  et  seq. 

Diet  in  relation  to  cancer  proclivity,  12, 
13,  14,  23,  25,  31,  35,  41,  42,  43,  59,  64, 
65,  66,  68,  70,  85,  86,  91,  92,  94,  212, 
214,  332,  345-347,  349,  353 

Digestive  system,  its  proclivity  to  cancer, 
380-382,  384,  391  ;  lymph-gland  dis- 
semination in  cancer  of,  417,  418,  422 
(Troisier's  symptom)  ;  metastases,  434, 
435,  436,  437 

Diminishing  diseases,  50 

Dissemination  of  cancer,  6;  local,  410  ;  by 
lymphatic  permeation,  411  ;  lymph- 
glandular,  412  ;  via  the  thoracic  duct, 
422  ;  general  dissemination,  426  ;  meta- 
stases of  epithelioma,  431  ;  their  pro- 
clivity for  the  liver,  441  ;  of  sarcoma, 
416,  438  ;  their  proclivity  for  the  lungs, 
441  ;  general  conclusions,  444 ;  the 
theory  of  metastasis,  442 ;  dissemina- 


tion of  non-malignant  tumours,  6,  426 ; 

of   quasi-malignant    tumours,    179,    187 

(Jensen's  mouse  tumour),  235,  241,  250 

(Sanfelice),  252  (Busse  and  Ciutis),  427  ; 

vide  also  Morphology 
Distribution   of   cancer   among   mankind, 

some  generalities,  13,  14,  21 
Dog,  great  proclivity  to  cancer,  94  ct  seq.  ; 

contagious  venereal  pseudo-plasms  of,  91, 

97,  179,  180,  181,  193 
Domestication  and  cancer  proclivity,   12, 

13,  14,  24,  58,  64,  66,  67,  88,  94,  118,  124 
Duhring's  neoplasm,  484 

I  EARLY  LIFE,  cancer  in,  90,  316,  317,  318, 

323,  324,  325  et  seq. 
.  East  End,  cancer  proclivity  of,  17,  26,  61, 


Edinburgh,  cancer  death-rates,  27,  69 

Egypt,  the  extreme  rarity  of  cancer  among 
the  aborigines,  42 

Embryonic  development  and  neoplasia, 
131,  132,  134  et  seq. 

Emphysema  in  the  cancerous,  340 

Endocytes  of  cancer  cells,  218, 219, 237-254, 
405 

England  and  Wales,  cancer  incidence,  25, 
26,  30,  51  et  seq.,  79 

Environment  in  relation  to  cancer  mor- 
tality, 12-21,  30,  32,  58,  62,  66,  68,  85, 
88,  134 

Enzymes  of  cancer,  6,  8,  9,  208,  215,  219, 
228,  408 

Epidemic  cancer,  85,  109,  187,  188,  195, 
263-269 

Epithelioma,  definition  of,  10,  155,  164, 
165,  379  (site  incidence),  394  (statistical 
tables)  ;  morphology  of,  400  et  seq.  ; 
322  (as  to  age  and  sex)  ;  290,  294,  295, 
330  ;  bilateral  forms,  298  ;  multiple,  302  ; 
in  animals,  89  ;  physiological  properties 
of,  18,  156,  157,  231,  403,  409,  414 

Epithelium,  the  typical  cell,  209 ;  "rests"  of, 
147,  150,  151,  Io5  ;  grafting  experiments 
with,  169 ;  growth  of,  in  blood-serum 
and  agar,  173  ;  atypical  proliferation  of, 
5,  124,  173,  249,  252,  255,  262,  480 
et  seq.  ;  traumatic  dermoids,  170-172  ; 
proliferation  of,  in  process  of  repair,  172, 
173,  174  ;  epithelial  pseudo-plasms,  174, 
187  ;  epithelioses,  174,  181  ;  varied 
growth  of,  with  age,  327,  330  ;  causative 
factors  of  its  growth,  215  ;  proclivity  of 
epithelial  structures  to  cancer,  377 

Erosions  of  os  uteri,  cancerous  appearance 
of,  5,  159,  174 

Erysipelas  and  cancer,  342,  488,  496 

Europe,  distribution  of  cancer  in,  21,  22, 
24 ;  cancer  death-rates  of  the  chief 
communities,  25  ;  rarity  of  cancer  along 
the  Mediterranean  littoral,  25  ;  in  the 
capital  cities  and  large  towns,  27  ; 
highest  and  lowest  rates,  25,  27  ; 
aetiological  factors,  25  ;  urban  and  rural 
incidence,  27,  28,  29,  68 

Experimental  cancer  research,  169 
(Chap.  VIII.)  ;  with  the  contagious 
venereal  malady  of  dogs.  179 ;  with 
32—2 


500 


INDEX  OF  SUBJECTS 


Jensen's  mouse  pseudo-plasm,  187  ;  ex- 
periments with  normal  tissue  elements, 
169 ;  with  warty  and  condylomatous 
tumours,  177  ;  with  malignant  tumours, 
181  ;  grafting  human  tumours  into 
animals,  182  ;  grafting  between  animals 
of  the  same  species,  187  ;  between 
animals  of  different  species,  194  ;  trans- 
mission of  cancer  between  human 
beings,  194,  195  ;  between  husband  and 
wife,  196,  197  ;  auto-implantation  of 
cancer  in  human  beings,  197  ;  auto- 
implantation  of  warts,  177 

Extrinsic  causative  factors  of  cancer,  the 
question  of,  133,  214, 216,  229  (inicrobes),   : 
270   (inflammation),    283    (syphilis   and 
smoking),  282  (Paget's  disease),  90,  286 
(trauma) 

Eye,  tumours  of,  95,  98,  99,  100,  101,  104,  j 
106  (in  animals) ;  heredity  of  melanotic 
sarcoma,  361,  of  glioma,  362,  in  twins,  j 
362  ;  sarcoma  of  choroid,  419,  427,  429,  i 
439,  461,  467  ;  rnetastatic  epithelioma  i 
of,  432 

FAMILY  HISTOBY,  356  (Chap.  XVII.) ;  in-  ! 
stances   of    multiple    family    cancer,  in   | 
breast    (358),    uterus    (360),    gastro-in-   i 
testinal  (360),  external  genitalia  (361),   i 
eye    (361),    glioma    (362)  ;    cancer   and   ; 
tumours  in  twins  (362)  ;  heredity  of  non-   ' 
malignant    tumours    (363)  ;    homotopic 
transmission     (364)  ;      family      history 
analyses  (365) ;  general  considerations  as 
to  cancer  inheritance  (366)  ;  hereditary   ; 
proclivities  correlated  with  cancer  (370) ; 
the  Middlesex  Hospital  fiasco,  367 

Fatty  changes  in  cancer  structures,  405,  | 
490,  450  ;  fatty  degeneration  of  cachexia,  : 
475 ;  obesity  and  cancer,  333  ;  fatty  < 
tumours  in  animals,  92,  97,  102,  105,  i 
106,  111 

Fecundity-  of  cancer  patients,  66,  67,  353  ; 
in  family  history,  373 ;  twinning  and 
cancer,  374 

Ferments  of  cancer,  question  of,  208,  215,  '< 
219,  228,  408 

Fertilization  and  nutrition,  208,  353 ;  arti-    ' 
ficial,  209  ;  self-fertilization  of  tissue  cells 
as  cause  of  cancer  genesis,  218 

Fever,  its  comparative  rarity  and  slight  i 
intensity  in  cancer,  477 

Fish,  tumours  of,  113 

Foetus  in  fcetu,  the  type  of  tumour  forma- 
tion in  excdsis,  140 

Food  in  relation  to  cancer,  14,  19,  26,  43, 
59,  61,  63,  65,  66,  67,  68,  94,  119,  135, 
332,  349  ;  vide  also  Moat  consumption 

France,  high  cancer  death-rate  of,  24,  25, 
27  (Paris),  29  (towns  of),  72  (increase  of 
cancer  and  conditions  of  existence) 

Frog,  tumours  of,  113 

GALLS  and  other  vegetable  pseudo-plasms, 

125 
Gall-stones  and  cancer  of  the  gall-bladder, 

280  ;  proclivity  of  the  cancerous  to,  336     i 
Gastro-intestinal     tumours,     quasi-maliii-    j 


nant  forms,  485,  486  ;  heredity  of  cancer 
of,  360  ;  site  incidence,  384  ;  dissemina- 
tion of  cancer  of,  417,  418,  42.5,  434, 
435,  436 ;  initial  multiplicity  of,  306  ; 
rarity  of,  in  animals,  89 

Gemmation  and  tumour  formation,  26,  115, 
119,  138,  139,  140,  207 

Genesis  of  cancer,  129  (Chap.  VII.)  ;  his- 
.torical  review  of,  129  ;  extrinsic  or  in- 
trinsic, 133 ;  intrinsic  pathogenesis, 
134  ;  the  role  of  "  rests,"  139  ;  of  uterine, 
tumours,  144 ;  of  mammary  tumours, 
165  ;  experimental  study  of  cancer 
genesis,  169  (Chap.  VIII.)  ;  of  vegetable 
tumours,  119;  microbic  theory  of,  229 
(Chap.  X.) ;  inflammation,  trauma,  and 
other  extrinsic  factors,  270  (Chap.  XI.) 

Geneva,  cancer  mortality  of,  27,  55 

Geographical  distribution  and  incidence  of 
cancer,  12  (Chap.  II.)  ;  race,  complexion, 
and  conditions  of  existence,  14  ;  general 
survey  of  world-wide,  21  ;  in  Europe, 
24  ;  Asia,  30  ;  Australasia  and  Oceania, 
40 ;  Africa,  42 ;  America,  46 ;  topo- 
graphical, 79  (Chap.  IV.) 

Geological  configuration  and  cancer,  83,  84, 
85 

Germany,  cancer  incidence  of,  25,  27,  29, 
74  (increase  of)  ;  life  insurance  data  as 
to  increase,  51 

Germ  cells  and  somatic  cells,  117,  135,  13(J, 
213  ;  tumour  germs  and  ova,  9,  134,  139, 
201,  212,  214 

Glasgow,  cancer  death-rate  of,  69 

Glioma,  heredity  of,  362  ;  dissemination  of, 
439 

Glycogeu  in  relation  to  cancer  growth,  Jo'J, 
334,  408,  473,  496 

Goat,  tumours  of,  107 

Grafting  experiments  with  normal  tissues, 
169  ;  with  cartilage,  175  ;  with  uterine 
mucosa,  159 ;  with  ovary,  175,  176 ; 
with  teeth,  176 ;  with  cock's-spur, 
171  ;  human  cancer  into  animals,  182  ; 
cancer  grafting  between  animals  of  the 
same  species,  180  (with  non-malignant 
tumours),  187  ;  with  Jensen's  mouse 
tumour,  187  ;  with  the  contagious 
venereal  pseudo-plasm  of  dogs,  179  ; 
with  the  contagious  pseudo-plasm  of 
rats,  192  ;  between  animals  of  different 
species,  194 ;  with  cancer  between 
human  beings,  195,  196 ;  with  melanoma, 
185;  with  warts,  177 

Grief,  anxiety,  and  mental  distress  as 
causes  of  cancer,  345 

Growth  in  relation  to  cancer,  3,  4,  26, 
119,  132,  137,  139,  353  ;  infiltration, 
5,  202,  212  ;  cancer  growth  essenti- 
ally a  disintegrative  process,  213 ; 
causative  factors  of,  207  ;  in  relation  to 
nutrition,  212,  214  ;  in  relation  to  in- 
flammation, 270  ;  in  relation  to  meta- 
bolism, 215  ;  cancer  and  tumour  growth 
in  relation  to  growth  in  general,  201 
(Chap.  IX.)  ;  in  relation  to  growth 
ab  ovo,  216,  385  ;  in  cells,  202;  in  multi- 
cellular  organisms,  206  ;  tumour  growth, 


INDEX  OF  SUBJECTS 


501 


'213  ;  growth,  repair,  regeneration,  and 
tumour  growth,  220  ;  heteromorphosis, 
225  ;  the  question  of  trophic  nerves,  385 

HAMPSTEAD,  high  cancer  and  low  tubercle 
mortality  of,  59,  60,  61 

Healing  of  cancer,  484,  488-496 

Health  of  cancer  patients,  66,  67,  332,  341, 
348 

Herbivora,  prone  to  tubercle,  but  not  to 
cancer,  91 

Heredity  of  cancer,  examples  of,  358 
(breast),  360  (uterus),  360  (gastro-in- 
testinal),  361  (penis),  361  (eye),  362 
(glioma),  362  (miscellaneous),  362  (in 
twins),  363  (in  animals),  363  (non- 
malignant  tumours),  364  (homo topic), 
365  (family  history  analyses),  366 
(general  conclusions),  367  (Middlesex 
Hospital  fiasco),  369  (atavism),  370 
(hereditary  proclivities  correlated  with 
cancer),  371  (tubercle),  372  (insanity), 
372  (apoplexy),  373  (longevity),  373 
(fecundity),  374  (twinning  and  cancer), 
374  (Mendelism  and  cancer  heredity) 

Heterotopia,  147  (in  uterine  epithelium), 
155  (in  uterine  cancer),  148,  149,  150, 
151  (in  uterus),  167  (mammary),  409 
(primary  epithelioma  of  bone),  96  (in 
canine  mammary  tumours) 

Heteromorphosis  in  relation  to  tumour  for- 
mation, 225 

Highest  cancer  death-rates,  27 

Histioid  tumours  (somatogenic),  141 

History  of  cancer  genesis,  129 

Holland,  incidence  of  cancer,  27,  29,  73,  74 

Hong  Kong,  incidence  of  cancer,  30,  31 

Horse,  cancer  and  tumours  of,  99 

House,  alleged  infection  of,  by  cancer, 
263  et  seq. 

Humoral  theory  of  cancer,  129 

Hungary,  the  low  cancer  and  high  tubercle 
mortality  of,  25,  75 

Hydra,  regeneration  of,  7,  26,  222,  223, 
476  (as  type  of  recurrence) 

Hyperplasia,  and  not  inflammation,  the 
starting-point  of  cancer,  132,  136,  137, 
270,  410  (precancerous) 

ICELAND,  cancer  incidence,  20 

Immigrants,  undue  cancer  proclivity  of, 
14,19,20,32,33,41,78 

Implantation  experiments,  vide  Grafting 

Incidence  of  cancer,  vide  Geographical 
distribution 

Increase  of  cancer,  50  (Chap.  III.) ; 
experience  of  Scottish  Widows'  Life 
Assurance  Fund,  and  of  German  Life 
Assurance  Company,  51  ;  its  reality, 
52  ;  statistical  summary  of,  for  England 
and  Wales,  51,  53;  for  Scotland,  67; 
for  Ireland,  70  ;  for  Switzerland,  70  ;  for 
Denmark,  71  ;  for  France,  72 ;  for 
Sweden  and  Norway,  73  ;  for  Germany 
and  Prussia,  74  ;  for  Austria  and  Hun- 

tary,  75  ;  for  Italy,  75  ;  for  the  United 
tates,  76  ;  for  Australia,  77  ;  and  for 
New  Zealand,  78  ;  the  disproportionate 


increase  among  men,  57  ;  the  concom- 
itant decline  of  tubercle,  58 ;  aetiological 
indications,  62  ;  influence  of  sudden 
change  of  environment  on,  62  ;  in  im- 
migrants, 14,  19,  20,  32,  33,  41,  78; 
progressive  population  as  a  concomitant 
of,  53,  69 ;  urbanization,  63  ;  pros- 
perity, 63 ;  good  food,  63,  64 ;  good 
sanitation,  60,  64,  66 

;  India,  the  comparative  rarity  of  cancer  in, 
23  ;  the  poverty  and  dietetic  abstemious- 
ness of  the  natives,  23  ;  the  incidence 
and  localization  of  cancer  in,  33-40  ;  the 
Kangri-burn  "cancer,"  34,  36;  the  rela- 
tive proclivity  to  "  cancer  "  of  the  penis, 
35,  36,  38,  39 ;  betel-chewing  and  buccal 
"  cancer,"  39  ;  Ceylon,  39 

;  Induratio  benigna,  apt  to  be  mistaken  for 
cancer,  480 

;  Industrialism,  as  a  predisposing  cause  of 
the  increase  of  cancer,  62,  65 

.  Infectiousness  of  cancer,  the  question  of, 
24,  262  ;  as  between  human  beings,  194  ; 
auto-inoculability  of,  197  ;  general  con- 
clusions as  to  infection,  269  ;  infectious 
and  suppurative  diseases  in  the  can- 
cerous, 342,  343,  344 

Infiltration,  as  a  characteristic  of  cancerous 
growth,  5,  202,  212,  215,  219,  227,  228, 
401,  402  (due  to  a  special  kind  of  meta- 
bolism), 408,  442,  443 

Inflammation,  the  question  of  its  relation 
to  cancer  and  tumour  formation,  270  ; 
the  Broussaisian  theory,  119,  130  (vide 
also  under  Chronic  inflammation)  ;  pre- 
cancerous  conditions,  272  ;  mastitis  and 
mammary  cancer,  274  ;  Paget's  disease, 
282  ;  laceration,  endometritis  etc.,  and 
uterine  cancer,  275  ;  gastric  ulcer  and 
gastric  cancer,  279 ;  gall-stones  and 
cancer  of  the  gall-bladder,  280  ;  phimosis 
and  cancer  of  the  penis,  281  ;  "  lupus 
cancer,"  283 ;  leucoplasia,  syphilis, 
smoking,  in  relation  to  lingual  and 
buccal  cancer,  283  ;  trauma  and  cancer 
286  ;  traumatic  malignancy,  287  ;  in 
flammation  of  cancerous  tumours,  487 
proclivity  of  the  cancerous  to  inflamma 
tory  diseases,  344  ' 

!   Inheritance  of  cancer,  vide  Heredity 

;  Initial  seats  of  cancer  and  tumours,  89 
(in  animals),  375  (in  humanity)  ;  statis- 
tical tables,  377-382,  386-387,  391,  394- 
399  ;  the  proclivity  of  certain  regions  of 
particular  organs,  382  ;  in  congenital  and 
early-life  tumours,  325  ;  the  question  of 
trophic  nerve  influence  in  localization, 
385  ;  localization  of  tumours  in  Indian 
population,  33-40 ;  initial  multiplicity, 
298  ;  no  marked  change  in  site  incidence 
of  cancer  during  the  last  half-century, 
55,  56 

Insane,  rarity  of  cancer  in  the,  344,  345  ; 
increase  to  insanity,  50,  66,  68 ;  pro- 
clivity to  insanity  in  the  family  history 
of  the  cancerous,  372 

Intemperance,  in  relation  to  cancer,  67, 
351 


502 


INDEX  OF  SUBJECTS 


Intestine,  site  incidence  of  cancer,  384,  387  ;   j 
dissemination     of    cancer,     436,     437  ;   j 
quasi-malignant    disappearing    tumours 
of,  486  ; 

Intrinsic  pathogenesis  of  cancer,  133,  134 
et  seq.,  212,  214,  216, 

Invertebrata,  tumours  of,  91 

Ii eland,  the  low  cancer  and  high  tubercle 
mortality  of,  25,  27,  28,  65,  69,  70  ;  the   : 
low  cancer  death-rate  of  poverty-stricken   j 
Kerry,  where  the  tubercle  mortality  is  | 
exceedingly    high,    65,    70 ;    the    high 
cancer  death-rate  of  well-to-do  Ulster, 
28,  70 

Italy,  the  low  cancer  death-rate  of,  25,  75 

JAMAICA  and  the  West  Indies,  the  rarity  | 
of  cancer  among  the  negroes,  47,  48 

Japan,  cancer  mortality  of,  22,  32 

Jensen's  mouse  tumour,  its  non-cancerous   , 
nature  indicated,  187  ;  epidemic  occur- 
rence and  contagiousness  of,  188  ;  im-    ! 
plantation  experiments  with,  190  ;  para- 
sites of,  188,  189  ;  compared   with   the 
contagious  venereal  pseudo-plasm  of  dogs,   ; 
189  ;   rats  subject  to  a  similar  pseudo- 
plasm,  192 

Jews,  cancer  incidence,  with  special  refer- 
ence to  the  conditions  of  existence,  14. 
16,  17,  18,  19 

KANGRI-BURN  "  cancer,"  34,  36 

Kaposi's  disease,  484 

Kerry   and    the    "Wild    West,"    the   low 

cancer  and  high  tubercle  mortality  of, 

65,  70 

Knaurs  and  tumours  of  trees,  120 
Krukenberg's  ovarian  tumours,  307,  436 

LARYNX,  the  question  of  cancer  arising  from 
non-malignant  tumours  of,  296,  297  ; 
auto-inoculation  of,  199 

Leucoplasia,  in  relation  to  cancer  of  the 
tongue  and  mouth,  283,  284,  285 

Life-history  of  cancer  patients,  setiological 
indications  derived  from  study  of,  66,  67, 
332  (Chap.  XVI.) 

Life  insurance  data,  as  to  the  increase  of 
cancer,  51,  54,  56 

Lion,  cancer  in  a  captive,  110 

Lip,  cancer  of,  auto-inoculability,  199  ; 
with  leucoplasia,  285  ;  influence  of  sex, 
315,  316  ;  influence  of  age,  322  ;  relative 
frequency  of,  379-381  ;  dissemination  of, 
417,  434  (metastases) ;  healing  of,  489  ; 
lymph-glandular  dissemination  of,  with- 
out obvious  primary  lesion,  426 ;  in 
relation  to  occupation,  355 

Lipoma,  heterotopic,  148  ;  site  incidence  of , 
389,  394-399  ;  alleged  dissemination  of, 
427  ;  in  animals,  92,  97,  102,  105,  106,  111 

Localization  of  cancer,  vide  Initial  seats  of 

London,  cancer  mortality  of,  17,  27,  29, 
60  (increase  of  cancer,  decline  of  tubercle, 
1851  to  1905),  61,  79-82,  86 

Lowest  cancer  death-rates,  in  Europe,  25, 
27  ;  in  England,  66,  79,  80-83,  85,  86  ; 
.  in  Scotland,  28,  68,  69 


Lunatics,  small  cancer  proclivity  of,  vide 

Insane. 
"  Lupous    cancer,"  283  ;    epithelioma-like, 

483 

MALARIA,  the  alleged,  antagonism  with 
cancer,  340 

Males,  more  prone  to  cancer  than  females 
in  Australia,  41,  71  ;  in  New  Zealand, 
41,  78  ;  in  Norway  and  Switzerland,  315  ; 
the  disproportionate  increase  of  cancer 
among  males,  313,  57  (in  England  and 
Wales)  ;  68  (in  Scotland) ;  70  (in  Ire- 
land) ;  71  (in  Australia)  ;  78  (in  New 
Zealand)  ;  73  (in  Sweden) 

Malformations,  in  relation  to  cancer,  24, 
50,  139,  372 ;  uterine  tumours  and 
"  rests,"  144  ;  and  gross  developmental 
irregularity  of  the  uterus,  160  ;  mam- 
mary tumours  and  developmental  ir- 
regularity, 165 

Malignancy,  a  term  used  to  cover  a  multi- 
tude of  effects,  4-9  ;  characters  of  malig- 
nant tumours,  8,  9  ;  the  question  of  the 
origin  of  malignant  from  non-malignant 
tumours,  289  (Chap.  XIII.) 

Malignin,  the  hypothetical  cancer  ferment, 
219,  408 

Mammary  tumours,  the  genesis  of,  in  rela- 
tion to  developmental  irregularity,  165  ; 
nbro-adenoma,  167  ;  osseous  and  carti- 
laginous, 166-168  ;  dermoids,  168  ;  the 
question  of  the  origin  of  cancer  from 
non-malignant  tumours,  294.  Vide  also 
Breast  cancer 

Market  Deeping,  the  cancer  mortality  of, 
during  the  early  part  of  the  eighteenth 
century,  51 

Marriage  in  relation  to  cancer  proclivity, 
274,  275,  348,  353  ;  diet  in  relation  to 
fertility,  353 

Materies  morbi  of  cancer,  the  search  for, 
219 

Meat  consumption,  in  relation  to  cancer 
prevalency,  14,  19,  23,  41,  43,  46,  64,  66, 
68,  73,  75,  76,  78,  91,  92,  74,  214,  349, 
353  ;  vide  also  Alimentation 

Mediterranean  Littoral,  rarity  of  cancer, 
22,  25,  27 

Melanoma,  95,  96  (dogs),  98  (cat),  99,  100 
(horse),  104  (ox),  143  (moles  and  naevi 
as  germs  of),  152,  153  (uterine),  168 
(mammary),  185,  186  (grafting  experi- 
ments with),  361  (heredity  of  choroidal 
melano-sarcoma),  387  (site  incidence), 
419  (rarity  of  dissemination  of  choroidal 
melano  -  sarcoma  in  the  lymphatic 
glands),  426  (dissemination  of  melanotic 
staining),  427,  429,  439  (metastases), 
461,  467  (tardy  metastatic  recurrence 
of  choroidal  melano  -  sarcoma),  484 
(Kaposi's  disease — "  sarcoma  melanodos 
cutis  ")  ;  anomalies  of  recurrent  growths, 
466 

Mendelism  and  cancer  heredity,  374 

Menstruation  and  cancer,  348 

Metagenesis,  207,  214 

Metaplasia,  the  doctrine  of,  refuted,  141 


INDEX  OP  SUBJECTS 


503 


Metastasis,  vide  Dissemination 

Microbic     theory     of     cancer,     133,     229   '• 
(Chap.  X.),  233  (bacteria),  237  (protozoa)   ' 
249     (blastomycetes),     260     (mould-like 
fungi),  262  (the  question  of  infection),   ; 
197  (auto-inoculability)  ;  in  animals,  91,    '• 
97,   103,   105,   107-109,   112,   113,   183  ; 
in   dogs,    179,    180,    181,    193;  Jensen's   ; 
tumour,    187  ;    rat    pseudo-plasm,  186,   ' 
192  ;  melanotic  pseudo-plasms,  185,  186     ; 

Microscope,  invention  and  utilization  of, 
for  tumour  research,  130 

Mitosis  of  cancer  cells,  9,  172,  173,  210,  : 
219  (heterotypical),  227,  231,  242,  244,  j 
404  ;  vide  also  Centrosomes 

"  Mixed  "  malignant  tumours,  95,  98,  148,    j 
152,  154,  155,  158,  167,  168,  308  (sarco- 
epithelioma) 

Monkey,  the  almost  complete  immunity 
from  cancer  and  non-malignant  tumours, 
92,  93  ;  the  great  proclivity  to  tubercle, 
93,94 

Monks,  the  reputed  rarity  of  cancer  in 
monasteries  with  a  frugal  regimen,  347 

Morbus  miserice,  the  doctrine  that  cancer 
is  a  disease  of  this  class  is  refuted,  65-67 

Morocco,  rarity  of  cancer  among  the  : 
aborigines,  43 

Morphology  of  cancer,  400  (Chap.  XIX.), 
400   (the   primary   tumour),    410   (local   '. 
dissemination),     411,     446     (lymphatic 
permeation),  412  (lymph -glandular  dis- 
semination), 422  (dissemination  vi&  the 
thoracic  duct — Troisier's  symptom),  426 
(general  dissemination),  431  (the  metas- 
tasis of  epithelioma),  431   (mammary), 
432  (uterine),  433  (prostate),  427  (thy-   ! 
roid),  434  (lip,  tonsil,  oasophagus),  435   i 
(stomach),    436    (colon),    437    (rectum,   j 
pancreas),  438  (metastasis  of  sarcoma),   j 
440  (general  conclusions),  442  (theory  of   , 
metastasis)  ;     448     (the     varieties     of 
epithelioma),    448    (acute    forms),    449   . 
(chronic    forms),    454   (recurrence),  229  j 
(microbes  of — Chap.  X.) 

Mouse,  tumours  and  pseudo-plasms  of,  108,  ' 
109  ;  Jensen's  tumour,  187 

Mule,  tumours  of,  103 

Miiller,  J.,  his  theory  of  tumours,  131,132     ! 

Multiple  primary  cancer,  298  (Chap.  XIII. ).  : 
208  (bilateral  forms),  302  (skin),  303  i 
(uterus),  304  (mamma),  306  (gastro-  \ 
intestinal),  308  (mixed  malignant  j 
tumours),  310  (the  association  of  malig-  | 
nant  with  non-malignant  tumours),  307 
(general  conclusions) 

Muscles,  the  immunity  of,  from  primary 
and  secondary  cancer,  379,  387,  394- 
399,  447,  431-440  (secondary) 

Mutations,  sports  and  tumours,  3,  118-125, 
134,  212-214 

Myoma  of  the  uterus  and  "  rests,"  144  ; 
uterine  myomatosis,  145;  myoma  and 
gross  developmental  irregularity  of  the 
uterus,  etc.,  160;  heterotopic  structures 
in  myoma,  147  (epithelial),  148  (fatty), 
148,  149  (osseous,  cartilaginous,  calci- 
fying, and  fibrifying)  ;  heredity  of,  361 


,  moles  etc.,  as  tumour  "rests,"  143  ; 
vide  also  Melanoma 

Xatal,  the  immunity  of  the  natives  from 
cancer,  its  frequency  among  the  Boers 
and  European  residents,  46 

Natural  history  of  cancer,  meaning  of  the 
term  as  employed  in  this  work,  2 

Negroes,  cancer  proclivity  of,  in  relation  to 
the  conditions  of  existence,  14-16  ;  tho 
comparative  immunity  in  their  African 
homes,  42-44  ;  in  the  West  Indies,  47, 
48  ;  in  the  United  States,  14,  15,  76  ; 
rarity  of  cancer  of  the  penis  in,  not- 
withstanding their  great  proclivity  to 
phimosis,  282 

New  Zealand,  rarity  of  cancer  among  the 
aborigines,  40,  41 ;  its  incidence  and 
increase  among  the  whites,  40,  41 ,  78  ; 
proclivity  of  immigrants  to  cancer,  41,  78 

Non-malignant  tumours,  the  question  of 
the  origin  of  cancer  from,  289  (Chap. 
XII.)  ;  in  association  with  cancer,  310  ; 
genesis  of,  144-153,  160-163,  166-168; 
grafting  experiments  with,  177,  180 ; 
site  incidence,  389  ;  in  animals,  92-114  ; 
in  trees,  119  ;  heredity  of,  363  ;  recur- 
rence of,  7,  461  (especially  of  ovarian 
cystoma) ;  the  question  as  to  their 
dissemination,  426  (especially  as  to  thy- 
roid adenoma),  426 

North  America,  cancer  proclivity  of 
aborigines  in  relation  to  the  changed 
conditions  of  existence,  14,  16,  22,  46,  47 

Norway,  cancer  in,  20,  25,  27,  29,  30,  73 
(as  to  increase) 

Nucleus  of  the  cancer  cell,  4,  173,  217 
(heterotypical),  204,  205,  206,  210,  211, 
217-219,  231,  244,  403-405;  vide  also 
Mitosis 

Nuns,  alleged  immunity  from  cancer  in 
some  convents,  347 

Nutrition  in  relation  to  cancer  and  tumour 
growth,  3,  4,  12-14,  22-26,  43,  62,  64, 
66,  119,  124  (tree  tumours),  135,  203- 
205,  214,  330-332,  349,  353 

OBESITY  in  relation  to  cancer,  332,  333 

Occupation  and  cancer  proclivity,  354 

(Esophagus,  multiple  cancer  of,  199,  306, 
308  (sarco-epithelioma) ;  site  and  sex 
incidence,  381,  384 ;  dissemination  of,  434 

Osteitis  deformans,  its  kinship  with 
myeloma  rather  than  with  cancer,  335 

Ova,  compared  with  tumour  germs,  9,  134, 
139,  201,  212,  214,  221,  385  ;  compared 
with  buds,  116,  117 

Ovary,  grafting  experiments  with,  172, 
175  ;  influence  of,  on  tumour  growth, 
215  ;  on  metastasis,  444  ;  Krukenberg's 
tumour,  its  significance,  436  ;  dissemina- 
tion of  cancer  of,  419,  437  ;  ovarian 
cystoma  and  cancer,  295  ;  recurrence  of 
ovarian  cystoma,  461  ;  castration  and 
cancer,  91,  100,  215,  464,  465  ;  heredity 
of  ovarian  cystoma,  364 ;  ovarian 
papilloma,  178,  296  (a  contagious  con- 
dyloma — sui  generis) 

Ox,  cancer  and  tumours  of,  104,  105 


504 


INDEX  OP  SUBJECTS 


PANCREAS,  site  and  sex  incidence  of  cancer 
of,  394-399  (rarity  of  primary  cancer 
of) ;  secondary  cancer  of,  426,  431-440  ; 
the  dissemination  of  cancer  of,  437  ; 
supra-clavicular  adenopathy  (Troisier's 
symptom)  with,  425  ;  physiological 
characters  of  cancer  of,  8,  9,  156,  157, 
231,  403,  414  ;  pancreatic  secretion,  its 
alleged  connexion  with  cancer  genesis, 
216,  408 

Papilloina,  grafting  experiments  with,  177  ; 
ovarian,   178,  296  ;  auto-inoculation  of, 
177  ;  of  dogs,  97,  179,  189  ;  contagious- 
ness of,  177 
Paralysed    parts,    their    immunity    from 

cancer,  348 

Parasitic  pseudo-plasms,  91  (animals),  97, 
179  (dog),  103  (horse),  105  (ox),  107 
(sheep),  108  (rabbit),  109,  187  (mouse, 
Jensen's  tumour  etc.),  109,  110,  192 
(rat),  111  (whale),  112  (bird),  113  (frog), 
114  (fish),  125  (vegetable  organisms, 
galls  etc.).  127  ("  ant  plants  ") ;  5,  36 
(Kangri-burn  "cancer"),  234  et  seq. 
(bacterial),  237  et  seq.  (protozoan),  249 
et  seq.  (blastomycetic),  260  (mould-like 
fungi),  480,  481,  485  (mistaken  for 
cancer),  174,  181,  252  (Busse  and 
Curtis'  cases),  427  (dissemination  of) 
Paris,  cancer  incidence,  27,  29,  72  (in- 
crease) 

Parthenogenesis,  as  a  mode  of  growth,  207 
Pauperism,  privation  etc.,  in  relation  to 
cancer  incidence,  17,  19,  25,  28,  65-68, 
85,  86,  346,  354 

Penis,  the  alleged  frequency  of  "  cancer  " 
of,  in  India,  34-36,  38,  39 ;  phimosis  and 
cancer  of,  281  ;  the  comparative  rarity 
of  cancer  of,  282  (especially  in  negroes), 
380,  381,  382,  394-399  (statistics) 
Permeation,  lymphatic,  410,  411,  446 
Phthisis,  decline  of  concomitant,  with 
increase  of  cancer,  50,  58  (England), 
60  (London),  61  (Bristol),  68  (Scotland), 
69  (Edinburgh),  71  (Switzerland,  Den- 
mark), 72  (France),  73  (Sweden),  74 
(Germany,  Holland),  75  (Austria,  Hun- 
gary, Italy),  76  (United  States),  77 
(Australia),  78  (New  Zealand);  337 
(tubercle  and  cancer),  370  (in  the  family 
history) 
Physiological  characters  of  cancer,  8,  9, 

156,  157,231,403,414 
Pig,   cancer   and   tumours   of,    105 ;   does 
swine  flesh   as   food   give   proclivity  to 
cancer  ?  19 
Placentation,      compared      with      cancer 

growth,  5,  6,  442-444 

Plasmodiophora  brassicce,  as  a  cancer  para- 
site, 128,  194,  237,  245,  246,  266 
Pleural  adhesions,  emphysema  and  cardiac 

changes,  in  cancer  patients,  340 
Polar  bodies  of  cancer  cells,  210,  218 
Population,  progressive,  concomitant  with 

increase  of  cancer,  52,  53,  69,  70-78 
Pre-cancerous    conditions,    272,     410    (in 
general),  273  (skin),  274,  282   (breast), 
275    (uterus),    279    (gastric    ulcer    and 


gastric  cancer),  280  (gall-stones  and 
cancer  of  gall-bladder),  281  (phimosis 
and  cancer  of  penis),  283  (lupus),  283- 
285  (leucoplasia,  syphilis,  smoking  and 
buccal  cancer),  286  (trauma  and  cancer), 
287  (traumatic  malignancy) 

Precocious  sexual  development  in  relation 
to  cancer,  216 

Predisposition  to  cancer,  332,  333,  356v 
358,  371,  372,  374,  312-316  (in  relation 
to  sex),  317-325  (in  relation  to  age),  325 
(congenital  and  early-life),  330  (resume) 

Premature  births,  as  a  concomitant  of  the 
increasing  cancer  mortality,  50,  88 

Prevention  of  cancer,  12,  14,  17,  19,  22,  23, 
24,  25,  26,  52,  58,  61-67,  80,  85,  86,  87, 
88,  91,  92,  119,  312,  313,  337-339,  356, 
357,  371,  374 

Prison  inmates,  rarity  of  cancer  in,  66,  345 

Prosperity  and  cancer  proclivity,  22-26, 
50,  59,  61-63,  65,  68 

Prostate,  rarity  of  cancer  of,  as  compared 
with  uterine  proclivity,  380,  381,  394- 
399  ;  dissemination  of  cancer  of,  416, 
433  ;  supra-clavicular  adenopathy  with, 
425  ;  intra-osseous  metastases,  433,  434, 
441,  446 

Prostitutes,  not  often  affected  with  cancer, 
67,  341 

Proteids,  excess  of  in  food,  in  relation  to 
cancer  proclivity,  13,  22-24,  64,  65,  91, 
214,  350,  353 ;  vide  also  Meat  con- 
sumption, and  Alimentation 

Protozoa,  as  cancer  parasites,  185,  237,  247 
I 

I  QUASI-MALIGNANT  pseudo-plasms,  479 
(Chap.  XXII.),  173,  174;  vide  also 
Parasitic  pseudo-plasms 

i  RABBIT,  tumours  and  pseudo-plasms  of, 
108 ;  alleged  artificial  production  of 
cancer  in,  Lack's  experiment,  172 

;  Race  in  relation  to  cancer  proclivity,  14, 
22,  23 

I  Rat,  cancer  and  other  tumours  of,  109  ; 
quasi-malignant  tumours  of,  110,  192 
(transplantation  experiments) ;  "  can- 
cer "  epidemics  in,  109,  188  ;  grafting 
non-malignant  tumour  in,  180 
Rectum,  site  incidence  of  cancer,  379-382, 
384,  388,  391,  394-399  ;  sex  incidence, 
316 ;  age  incidence,  321,  322 ;  epi- 
thelioma  of  in  early  life,  327  ;  sarcoma, 
325  ;  dissemination,  437 
Recurrence,  7,  455  (Chap.  XX.)  ;  early, 
456-458  ;  immediate,  458  ;  tardy,  459, 
460,  461  ;  long  immunity  from,  460,  461  ; 
of  non-malignant  tumours,  7,  227,  461 ;  of 
macrodactyle,  461  ;  alleged  of  redundant 
digits,  226  ;  of  ovarian  cystoma,  461-465  ; 
rationale  of,  465  ;  seminium  cellulare  as 
agents  of,  466,  467  ;  metastatic  recur- 
rence, 467  ;  repeated  recurrences,  458  ; 
date  of  supervention  of,  456,  457  ;  proto- 
types of,  7,  227,  467 

Regeneration  and  repair,  220,  221  (hydra) ; 
226,  227  (mankind);  221,  224  (am- 
phibians); 224  (triton);  225  (lizard); 


INDEX  OF  SUBJECTS 


505 


redundancy  and  regeneration,  225  ; 
heteromorphosis,  225  ;  similitude  of  the 
reparative  new  formation  to  cancer  in 
minute  structure,  172,  173,  227 
Reproduction,  cancer  as  a  phenomenon  of 
the  same  order  as,  3,  26,  118,  119,  134 
(tumour  formation  a  special  form  of 
overgrowth  of  the  individual),  212  (gem- 
mation or  agamogenesis  the  physiolo- 
gical paradigm  of  neoplasia),  214  ;  age 
incidence  of  cancer  and  decline  of 
reproductive  activity,  215,  216,  319,  320, 
330,  331,  353  ;  castration  and  cancer 
proclivity,  444,  464,  465  ;  in  animals, 
90,  100  ;  vide  also  Castration 
Reptiles,  tumours  of,  112,  113 
'Rests,"  as  tumour  germs,  133,  139  et  seq., 
143  (moles  and  nsevi),  144  (uterine),  165 
(mammary),  409 

Rheumatism  and  cancer,  67,  335,  336,  373 
Rhinoceros,  cancer  of  stomach  in,  110 
Rodent  ulcer,  initial  multiplicity  of,  302, 
303  ;  age  and  sex  incidence,  316,  322  ; 
author's  case  at  age  of  fourteen,  327  ; 
lymphatic  glands  in,  417  ;  site  incidence, 
385 

Rural  localities,  incidence  of  cancer  in,  22, 
30  ;  high  death-rates  in  small  Normandy 
villages,  27  ;  in  Australia,  41  ;  in  the 
United  States,  47,  76  ;  the  change  from 
rural  to  urban  life,  62-65  ;  in  Scotland, 
68,  69  ;  in  Ireland,  70  ;  in  France,  72 ; 
in  England  and  Wales,  79,  83,  85,  86  ; 
the  low  cancer  mortality  of  the  Mediter- 
ranean littoral  and  of  the  adjacent 
islands,  25,  27 

SALT  in  relation  to  cancer  causation,  350, 
351 

Sanitation  and  cancer  incidence,  W.  Farr's 
investigation  of,  60  :  the  experience  of 
Hampstead,  60,  61,  269  ;  Clifton,  61,  269  ; 
and  Bath,  268,  269 

Sarcoma,  definition  of,  10,  11  ;  site  inci- 
dence of  in  China,  31,  32  ;  in  India,  34- 
39  ;  in  England,  386-388,  391,  392,  394- 
399  ;  in  animals,  89,  90,  95  and  98  (in 
dog),  96  (cat),  100  (horse),  104  (ox), 
105  (pig),  106  (sheep)  ;  implantation 
experiments  with,  184-186,  192,  194  ; 
quasi-sarcomatous  pseudo-plasms,  252, 
253,  260,  484  ;  origin  of  from  non-malig- 
nant tumours,  292,  293,  294,  296  ; 
bilateral  forms,  299-302;  initial  multi- 
plicity, 303,  307  ;  sarco-epithelioma,  308  ; 
influence  of  sex,  312  ;  influence  of  age, 
323-330  ;  heredity  of,  360-363  ;  relative 
frequency,  376,  386  ;  dissemination  of, 
416,  418,  419,  438  (metastases)  ;  the 
lung  the  commonest  seat  of  metastasis, 
441  ;  withering  "  sarcoma,"  484,  485  ; 
relation  to  lymphatics,  407,  413  ;  vide 
also  Breast,  Uterus,  and  Choroid 

Savages,  rarity  of  cancer  and  tumours  in, 
12,  13,  14,  16,  21,  40,  43-46,  66,  87-88, 
92,  93  ;  vide  also  Aborigines 

Scotland,  cancer  mortality  of,  25,  27,  28, 
67,68 


Senility  in  relation  to  cancer  growth,  203- 
206  (senescence)  ;  cancer  not  a  senile 
disease,  318-320 ;  its  connexion  with 
decline  of  reproductive  activity,  90,  215, 

320,  330,   331  ;  vide  also  Reproduction 
and  Castration 

Sex  in  relation  to  cancer  and  tumour  pro- 
clivity, 41,  57,  58,  68,  70,  73,  77,  78,  312 
(Chap.  XIV.),  376;  in  animals,  90; 
defective  development  of,  associated 
with  cancer,  162  ;  cancer  and  decline  of 
reproductive  activity,  215,  216,  320, 
330  ;  ovarian  disease  and  cancer,  443,  462- 
465  ;  the  influence  of  sex  in  disease,  refer- 
ence to  author's  book  on,  280  ;  nutrition 
in  relation  to,  25,  26  ;  sexual  health  of 
cancer  patients,  66,  67,  332,  333,  348, 
353,  356  ;  vide  also  Reproduction  and 
Castration 

Sheep,  cancer,  tumours,  and  pseudo-plasms 
of,  106,  107 

Site  incidence  of  cancer  and  tumours,  373 
(Chap.  XVIII.),  391-393  ;  in  animals,  89  ; 
in  relation  to  sex  incidence,  54,  55,  56, 
312  (Chap.  XIV.),  90  ;  congenital  and  in 
early  life,  325;  in  India,  34-39;  in 
China,  31,  32  ;  vide  also  Localization 

Skin,  cancer  of,  reputed  frequency  of,  in 
India,  34  ;  precancerous  conditions  in 
relation  to,  272,  281,  282,  283  ;  site 
incidence  of,  377-382,  385,  388,  399  ;  in 
animals,  90  ;  age  and  sex  incidence,  316, 

321,  322,  327  (early  life)  ;  in  relation  to 
"  rests,"  moles,  nsevi  etc.,  143  ;    initial 
multiplicity,    301,    302 ;    melanoma    of, 
419  ;    dissemination    of,    417  ;    pesudo- 
plasms  of,  255,  256  (blastomycetic  der- 
matitis), 483-485 

Smoking,  in  relation  to  lingual  and  buccal 
cancer,  284,  285 

Somatic  cells,  the  question  as  to  specific 
distinction  between  them  and  germ 
cells,  117,  134-139,  141,  213,  223,  357  ; 
vide  also  Germ  cells 

Spain,  cancer  incidence,  25,  27 

Specificity  of  cancer,  the  question  of,  5-8, 
119,  131,  134,  214,  219,  226,  229-232, 
404,  406,  408,  409,  478 

Spermatic  influence  in  cancer  genesis,  218 

Spirochsetse  as  cancer  parasites,  188,  189, 
247 

Sports  in  relation  to  tumour  growth,  3, 
117,  118,  119,  134,  139,  214  ;  vide  also 
Mutation 

Stomach,  reputed  rarity  of  cancer  of,  in 
India,  34  ;  in  Egypt,  43  ;  and  in  animals, 
89  ;  increase  of  in  England,  54,  55  ;  old 
statistics  respecting  (Virchow  and 
d'Espine),  55  ;  alleged  artificial  produc- 
tion of  cancer  of  by  irritation  of  gastric 
ulcers,  173  ;  auto-inoculation  of,  199, 
436  ;  initial  multiplicity,  306,  307  ;  with 
non-malignant  tumours,  310  ;  cancer  of 
the  stomach  concomitant  with  adenoma 
of  both  adrenals,  310  ;  influence  of  sex, 
54,  55,  315  ;  influence  of  age,  321,  322  ; 
congenital  and  early  life  cases,  325,  328  ; 
in  advanced  age,  330  ;  gastric  ulcer  and 


506 


INDEX  OF  SUBJECTS 


gastric  cancer,  279;  heredity  of  (the 
Bonaparte  family),  360,  361  ;  site  inci- 
dence, 379  et  aeq.,  384,  387,  388  (sar- 
coma). 391-399  ;  physiological  characters 
of,  403,  414  ;  dissemination  of,  417,  418, 
4_'.">  (Troisier's  symptom),  434,  435,  436 
(intra-osseous) ;  secondary  cancer  of,  434  ; 
with  Krukcnborg's  ovarian  tumours, 
436  ;  quasi-malignant  tumours  of,  486  ; 
in  cachexia,  471,  474,  475  ;  with  acan- 
thosis  nigricans,  347 

Subungual  exostosis,  recurrence  of,  7, 
461 

Suppurative  maladies  in  the  cancerous, 
342  ;  suppuration  of  cancerous  growths. 
487 

Sweden,  cancer  mortality  of,  20,  25,  27,  29. 
30,  51  (Fellingsbro),  72,  73 

Switzerland,  cancer  mortality  of,  25,  27, 
29,  55,  70,  71 

Syphilis  and  cancer,  rarity  of  syphilis  in 
female  cancer  patients,  67,  341  ;  in  rela- 
tion to  lingual  and  buccal  cancer,  283 ; 
the  diagnosis  of  syphilis  from  cancer,  479, 
480,  485 

TEETH,  grafting  experiments  with,  176 

Temperate  climates  and  cancer  mortality, 
21,  22,  23,  24 

Terato-genesis  and  tumour  genesis,  139 
et  seq. 

Testis,  dissemination  of  cancer  of,  419  ; 
metastases  of,  434,  440 ;  relative  fre- 
quency of,  380,  381,  382,  388,  394-399 

Thyroid,  alleged  influence  of,  on  cancer 
genesis,  215,  216,  333 ;  comparative 
rarity  of  cancer  of,  394-399  ;  dissemina- 
tion of  thyroid  cancer,  416  ;  metastases 
of,  427  ;  initial  lesion  of,  428 ;  the 
question  of  metastasis  by  the  non- 
malignant  thyroid,  426 ;  intra-osseous  dis- 
semination of,  428  ;  resolution  of  mam- 
mary cancer  after  suppuration  of  goitre, 
494 

Thoracic  duct,  dissemination  of  cancer  by, 
422  (Troisier's  symptom) 

Tigress,  cancer  of,  110 

Tongue,  leucoplasia,  smoking  and  syphilis, 
in  relation  to  cancer  of,  283 ;  auto- 
inoculation  of  cancer  of,  199  ;  initial 
multiplicity  of  cancer,  306 ;  sex  inci- 
dence of  cancer  of,  54,  55,  315  ;  age 
incidence  of,  322  ;  cancer  of  in  a  cente- 
narian, 330  ;  site  incidence,  388,  385,  391- 
399  ;  dissemination  of  cancer,  417,  434  ; 
tardy  recurrence  of,  460  ;  healing  of,  491 

Tonsil,  relative  frequency  of  cancer,  394- 
399  ;  dissemination,  419,  434 

Topography  of  cancer,  13,  56,  57,  79 
(Chap.  IV.) 

Towns,  cancer  incidence  of,  26-30,  63,  66  ; 
London,  60  ;  Hampstead,  Clifton,  Bath, 
60,  61  ;  28,  69  (Scotland)  ;  29,  72  (Paris 
and  France)  ;  Prussia,  Bavaria,  and 
Saxony,  29  ;  Austria,  29,  75  ;  Norway, 
29,  73;  Holland,  29,  74;  Italy,  75; 
United  States,  76  ;  England,  27,  28,  60, 
61-66,  79-86,  354,  355 


Transplantation  experiments,  169-200 
(Chap.  VIII.)  ;  vide  also  Grafting 

Trauma,  in  relation  to  cancer  genesis, 
286,  287,  458,  459,  464,  465  ;  traumatic 
dermoids,  171  ;  development  of  cancer 
in  track  of  operation  wounds,  6,  426,  427- 
461,  463-465 

Trees,  cancer  and  tumours  of,  115 
(Chap.  VI.)  ;  their  relation  to  abnormal 
gemmation,  119;  galls,  125;  pseudo- 
plasms  due  to  parasitism  of  plastno- 
diophora  brassicse,  265,  266 

Trophic  nerves,  in  relation  to  cancer 
growth,  385 

Tropics,  rarity  of  cancer  in,  21-24 

Trypsin,  alleged  curative  effects  of,  216 

Tubercle  in  relation  to  cancer,  decline  of 
tubercle  mortality  with  increase  of  that 
from  cancer,  58-67  ;  in  Scotland,  68,  69  ; 
in  Switzerland  and  Denmark,  71  ;  in 
France,  72  ;  in  Sweden,  73  ;  in  Holland, 
Prussia,  and  Germany,  74  ;  in  Italy,  75  ; 
in  United  States,  76  ;  in  Australia,  77  ; 
in  New  Zealand,  78  ;  in  animals,  91  ;  in 
relation  to  diet,  63-66;  the  inter- 
relations of  tubercle  and  cancer,  337  ; 
in  the  family  history,  371  ;  in  England, 
59,  60,  61,  85,  86  ;  in  London,  60  ;  in 
Hampstead,  Clifton,  and  Bath,  61,  268 

Tumour,  definition  of,  2,  3,  134  (a  special 
form  of  overgrowth  of  the  individual)  ; 
kindred  processes,  3,  4,  119,  134,  21-2, 
220,  225  ;  may  arise  in  any  multicellular 
being,  12  ;  genesis  of,  133-143  ;  "  rests," 
143-168  ;  developmental  irregularity, 
160  ;  tumour  growth,  212,  216  ;  microbic 
theory  of,  229  ;  inflammation  and  tumour 
formation,  270 ;  question  of  origin  of 
malignant  from  non-malignant  tumours, 
289  ;  association  of  cancer  with  non- 
malignant  tumours,  310 ;  influence  of 
sex,  312  ;  of  age,  317  ;  site  incidence,  391- 
399  ;  family  history  of,  356  ;  vide  also 
Nutrition,  Conditions  of  existence,  and 
Environment 

Twins,  cancer,  tumours,  and  developmental 
anomalies  in,  362,  363 


;   ULCEKATION  of  cancer,  405,  489  (healing 

of) 

Ulster,  high  cancer  proclivity  of,  28,  65 
Urbanization  and   cancer  proclivity,   vide 

Towns 

Uterus,  increase  of  cancer  of,  54,  55  ; 
uterine  tumours  and  rests,  144  et  seq.  ; 
tumours  of,  and  developmental  irregu- 
larity, 160 ;  myomatosis  of,  145  ; 
myoma  and  rests,  144  ;  lipoma  of,  and 
fat  heterotopia,  148;  epithelial  rests, 
146  ;  dermoids,  151  ;  cancer  in  relation 
to,  155  ;  osseous  and  cartilaginous  rests, 
148  ;  cysts,  150  ;  endothelial  cysts,  153  ; 
sarcoma  of,  genesis  from  rests,  154  ; 
melanoma,  155  ;  epithelioma  and  epi- 
thelial rests,  155-160 ;  epidermoidal 
heterotopia,  158-160 ;  the  question  of 
marital  contagion  in  uterine  cancer,  190 
precancerous  conditions,  275  ;  myoma 


INDEX  OF  SUBJECTS 


507 


and  malignant  disease,  290  ;  initial  multi- 
plicity, 303  ;  association  of  with  non- 
malignant  tumours,  310  ;  sarco-epi- 
thelioma,  309  ;  site  incidence,  382,  391  ; 
age  influence  of,  315,  316,  321,  322,  328 
(early  life  cases),  330  (at  ninety-three)  ; 
menstruation,  348  ;  late  marriages, 
decline  of  birth-rate,  celibacy  etc.,  353  ; 
syphilis  and  uterine  cancer,  341  ; 
heredity  of,  360 ;  local  dissemination, 
411  ;  lymph-glandular  dissemination, 
417,  420;  metastases,  432,  433  (intra- 
osseous)  ;  Troisier's  sign,  425  ;  of  corpus, 
433  ;  acute,  452  ;  chronic,  452  ;  corroding 
ulcer,  455 ;  recurrence,  457  ;  tardy,  640  ; 
retrogressive,  494;  uterine  tumours,  refer- 
ences to  author's  book  on,  146,  149,  154, 
290,  317,  401,  429,  452,  463 

VAGINAL  tumours,  references  to  author's 
book  on,  154,  317 

Variation  and  tumour  formation,  3,  4,  24, 
26,  58,  62-67,  81,  92,  117,  119,  134-139. 
201,  202,  206,  212,  214,  221,  223,  225,  226 

Varieties  of  cancer,  448-453  ;  acute  forms, 
448,  452  ;  chronic,  449,  452,  453  ; 
atrophic,  450  ;  colloid,  450  ;  fatty  and 
caseating  types,  489,  490,  491 

Vegetable  organisms,  tumours  of,  115 
(Chap.  VI.)  ;  in  relation  to  bud  formation, 
119  ;  galls  and  pseudo-plasms,  115,  265  ; 
vide  also  Trees 

Vegetarianism  and  cancer  proclivity,  12, 
13,  14,  19,  21,  22,  23,  24,  25,  26,  28,  31, 
32,  36,  42,  43,  44,  45,  46,  48,  64,  65,  66, 
68,  69,  70,  91,  92,  212,  214,  332,  333,  337, 
345,  346,  347,  349,  350,  353,  354,  496  ; 
vide  also  Aborigines,  Savages,  Alimenta- 
tion, and  Nutrition 

Venereal  condyloma,  178,  179  (dogs),  296 
(ovarian) 


I   Villages,  cancer  mortality  of,  27,  28,  29,  70 

(Kerry),  71,  85,  86  ;  vide  also  Rural 
Virchow's  tumour  theory,  131,  132 

WAGES   in   relation   to   cancer   incidence, 

63-68 

Warts,     contagiousness     of,     177  ;     auto- 
inoculability  of,  177,  178  ;  transmission 
of,  by  experimental  implantation,  177 
Water,  in  relation  to  cancer  causation,  263, 
264,  265,  266,  352,  353 

I  Wealth,  in  relation  to  cancer  proclivity,  13, 
17,  21-24,  25-28,  50,  59-67,  68,  70-78,  85, 
86,  337,  353,  354 

I  Weismannism,  the  doctrine  of  specific  dis- 
tinction between  somatic  and  germ  cells 
refuted,  117,  134,  135,  136,  213,  223, 
357  ;  the  hereditability  of  cancer  and 
non-malignant  tumours  shows  that  ac- 
quired variations  may  be  inherited,  356- 

|  364  ;  Weismann's  neglect  of  the  evidence 
derived  from  pathology,  357 

'  West  Indies,  rarity  of  cancer  among  the 
negroes  of,  47,  48 

i  Wild  animals,  rarity  of  cancer  in,  87,  88, 
92  (monkey),  110,  113;  non-malignant 
tumours  in,  92 

:    Withering  sarcoma,  484,  485 

:  Woody  tumours,  120,  122,  123-125  ;  galls, 
126-128  ;  vide  also  Trees  and  Vegetable 
organisms 

i  Workhouse  inmates  and  cancer  proclivity, 
246 

|  World-wide  survey  of  the  distribution  of 
cancer,  21 

!  Wiirzbourg,  statistics  as  to  localization  of 
cancer  (1852-1855),  55 

YEAST  organisms,  as  cancer  parasites,  249, 
261  ;     vide     also     Blastomycetes     and 
|       Microbic  theory 


INDEX   OF   NAMES   OF   AUTHORS   CITED 


ABKL,  151,  309 

Abesser,  306 

Ackermann,  167 

Adami.  213 

Adamkiewicz.  231,  238  ,239 

Adams,  C.  K.,  40,  77 

Adams,  G.  T.  C.,  216 

Adams,  96 

Adler,  126 

Ahlfeld,  150,  152,  363 

Aitken,  299,  448 

Albarran,  237,  248 

Albere.  168 

Alessandri,  175 

Alexander,  164 

Algret,  163 

Alibert,  183,  195 

Allen,  77,  78,  152 

Allen.  C.  W.,  288 

Allingham,  327 

Amann,  164 

Amici,  130 

Andral,  130,  469 

Andriezen,  349,  417,  433 

Anseaux,  363 

Apolant,  189,  191 

Argenson,  477 

Arloing,  193 

Arnaudet,  263,  353 

Arnold,  S.,  167 

Arnott,  432,  445 

Ascher,  149,  293 

Aschoff.  354 

Ashby,  328 

Asken,  288 

Aslanian,  155 

Atthill,  360 

Auche,  474 

Aulton,  97 

Axe,  101,  106 

BABES,  147,  291,  425 

Bach,  150 

Bacon,  2 

Balfour,  A..  44 

Ballanco,  93,  183,  186,  217,  234,  238,  240, 

484 

Bard.  304,  307 
Barette,  151 
Barfurth,  140,  170 
Barker,  A.  E.,  284 
Barker,  F.,  452 
Barnes,  150,  329 
Barrier,  101 
Harwell.  287 


Bashford,  13,  57,  89,  92.  99.  100,  104,  105. 
112,  113,  114,  188,  191,  193,  318.  326 

Basso,  172,  176 

Bastianelli,  250 

Bataillon,  113 

Bateson.  W.,  134 

Battle,  167 

Bauby, 19 
;   Baumgarten,  234,  339 

Bayha,  283,  302,  485 

Bayle.  130,  197,  290,  311 

Bazin,  347 

Beadles,  304,  307 

Beard,  J.,  138,  140,  216,  408 

Beatson,  302,  343,  495,  496 

Beattie,  177 

Beddoe,  J.,  20 

Bedford  J.  S.,  153 

Beccari,  127 

Beck,  304,  306 

Becker,  303 

Behla,  43,  194,  195,  197,  263,  265,  266,  353 

Behold,  43 

Beigel,  329 

Belin,  425 

Bell,  R.,  333 

Bell,  W.,  114 

Benda,  219 

Bender,  291,  432,  445 

Beneke,  332,  408,  474 

Bennet,  H.  J.,  149,  333,  480 

Berard,  167 

Bergell,  408 

Berger,  163 

Bergmann,  199,  283 

Berry,  J.,  428 

Bert,  P.,  176,  187 

Bertillon,  J.,  26,  72,  353 

Bertolet,  98 

Beuttner,  453 

Bevan,  256 

Beyea,  151,  363 

Beyerinck,  126 

Bezanson,  486 

Bichat,  129,  130 

Bidder,  149,  293 

Bidwell,  97,  343,  495 

Biehl,  164 

Bierfrund,  470,  473 

Biett,  195 

Bigot,  340 

Billings,  J.  S.,  16 

Billroth,  132,  166,  167,  168,  177,  183.  270, 
271,  288,  298,  299.  300,  303.  329,  383, 
407,  411,  414,  433,  448,  488,  494 


508 


INDEX  OF  NAMES  OF  AUTHORS  CITED 


509 


Binswanger,  303 

Birch-Hirschfeld,  174,  175 

Birchmore,  96,  103,  111 

Birkett,  166 

Bizzozoro,  227,  440 

Blacker,  G.  F.,  465 

Blanchard,  344,  495 

Bland-Sutton,  92,  93,  101,  109,  110,  111, 

112,  1.13,  146,  162 
Bloodgood,  100 
Blum,  247 
Bluinenbach,  224 
Blumenthal,  219,  408 
Boas,  195,  259,  328,  334,  338 
Boerhaave,  129 
Bogdan,  475 
Boinet,  186 
Bellinger,  54 
Boni,  161 
Bomiett,  224 
Bonney,  V.,  217 
Bontor,  450 
Borchmeyor,  168 
Bord,  470 
Borelius,  486 
Borriier,  44 

Borrel,  174,  188,  189,  191.  218,  237,  244 
Borrowman,  85 
Borst,  168,  181,  306 

Bosc,  184,  185,  194,  195,  231,  240,  264,  307 
Bossi,  197 
Boucher,  311 
Boudin,  25 
Boveri,  205,  209,  213 
Bowlby,  167.  302 
Box,  C.  R.,  461,  467 
Boyco,  262 

Bra,  231,  260,  261,  262 
Braithwaite,  261,  351 
Brain  well,  B.,  430 
Brand.  197 
Brauha,  257 
Brault,  248,  259,  301 
Brcnnan,  41 
Brens,  153 
Breton,  99,  301 
Brewer,  169 
Bricsky,  153,  165 
Briggs,  330 
Brinton,  279,  349,  435 
Bristowe,  484 
Broca,   101,  260,  304,  356,  358,  3(54,  369, 

401,  493 
Brockbank,  336 
Brodie,  248,  409 
Brooks,  H.,  88,  95 
Brouardel,  338 
Broussais,  120,  130,  132,  348 
Bruaudet,  244 
Bruhat,  258,  259 
Brunot,  32 
Briinnings,  148 
Bruns,  277 
Bryant,  T.,  283,  294,  300,  305,  329,  330, 

460,  483,  490 
Bryk,  167 
Buchanan,  306 
Buuhcr,  306,  400 


Buchnell,  307 

Budd,  194,  195 

Buffett,  163 

Bullock,  216 

Bulstrode,  280 
!   Bunge,  350 
I   Bunting,  306 
'   Burckhardt,  150 

Busch,  148,  167,  483 

Busse,  110,   174,  181,   190,  252,  262,  437, 
485 

Butler-Smythe,  464 

Butlin,  285,  307,  326,  351,  367,  418,  419, 
426,  434,  438,  439,  440,  456 

Buxton,  357 

Buxton,  B.  H.,  408 

CABOT,  195,  471 

Cadeac,  102,  104 
:   Cadiot,  89,  95,  96,  99,  101,  105 
I   Calderini,  362 
I   Calkins,  189 
!   Calmann,  462 

Cambria,  167 
j   Cameron,  166 
j   Campbell,  476 
I  Campbell,  H.  J.,  92,  93 
!   Camper,  88 

Campiche,  283,  416,  431,  438 

Cantlie,  31 

Carbonell,  363 

Carini,  253 

Carmichael,  329 

Carmichael,  R.,  233 

Carnoy,  206,  209 

Cartez,  151,  163 

Castro,  434 

Cathelin,  97 

Cattin,  333 

Cattle,  237,  403 
|  Cavaillon,  436 
!  Cayley,  335 
'  Cazin,  172,  179,  186,  287 
!   Celsus,  271 
i   Chabry,  139 
!   Chambers,  283 

Chambert,  329 

Chandler,  178 
:   Chapuis,  445 
I  Charcot,  151,  335 
I   Charrin,  186,  260 
!  Cheatle,  385 

!   Chevalier,  130  » 

1  Chiari,  307,  311 
I  Childe,  361,  364 
!  Chisholm,  15 

Claisse,  163 
!   Clark,  161,  162 
i   Clarke,  167 

Clarke  (the  brothers),  453 

Clarke,  B.,  495 

Clarke,  J.  J.,  179,  238 

Claude,  339 
!   Claveria,  363 
I  Clay,  160,  161 
!   Clendenning,  340 
1   Clouston,  372 
I   Clowes,  188 


510 


INDEX  OF  NAMES  OF  AUTHORS  CITED 


Coate,  167,  429 

Coblonz,  147,  150 

Cock,  176 

Coe,  291 

Coen,  167,  305 

Coghlan,  77 

Cohen,  338 

Cohnhoiin    133,   139,   140.   142,   143,   144, 

175,  270,  271,  301,  428,  4cS7 
Cohnstein,  196 
Coker,  330 
Colby,  326,  418,  439 
Coley,  W.  B.,  260,  419 
Colin,  104 
Colle,  432 
Collinge,  91 

Collins,  E.  T.,  361,  363,  439 
Colwell,  H.,  281,  336,  418,  435,  436 
Comte,  1 
Condon,  171 
Conner,  363 
Cook,  44 
Cooper,  239,  329 
Cooper,  Astley,  47,  167,  178,  294,  337,  402, 

411,  481 
Cooper,  S.,  438 
Copeman,  S.  M.,  474 
Coquot,  100 
Cordes,  303 
Cordua,  339 
Corner,  387 

Cornil,  95, 99, 152, 156, 158, 168, 198, 237, 406 
Corselli,  251,  362 
Cotoni,  362 
Cotterill,  484 
Couillaud,  347 

Councilman,  5,  173,  409,  445 
Coupland,  S.,  432 
Courmont,  306 
Courtin,  200 
Couvelaire,  436 
Coyne,  166,  294 
Crawford,  339 
Creighton,  98 
Cripps,  H.,  198,  287,  327 
Crisp,  95,  98,  109,  111,  112,  113 
Critzmann,  372,  373,  374 
Crocker,  R.,  484 
Crone,  329 

Crookshank,  E.  M.,  232 
Crouch,  C.  P.,  490 
Cruveilhier,  106,   130,   145,   151,  160,  161, 

167,  279,  291,  348,  432,  436 
Cuffer,  475 
Cullen,  178,  311,  360 
Cullingworth,  178,  293,  328 
Cuneo,  417 
Curtis,  110,   174,  181,  183,  190,  252,  261, 

262,  427,  485 
Cutler,  305 
Cuvier,  136 
Czempin,  199 
Czerny,  300,  327 
Czerwenka,  150,  162,  164,  165 

DAGONET,  184 
Dalgetty,  37 
Dalton,  339 


D'Anna,  186 

Darier,  181,  237,  238 

Dartigues,  163 

Darwin,  C.,  1,  118,  127,  135,  136,  313,  350, 
357,  358 

Davaine,  114 

Davey,  448 
i   Davidson,  38 
i   Deansly,  311 

De  Backer,  258,  259 

De  Boinville,  102 

De  Bovis,  29,  58,  314 

Delage,  205 

Delbarre,  363 

Delbet,  283 

Delepine,  186,  237,  239,  260 

Delore,  262 

Delpage,  153 

Demarquay,  197 

De  Morgan,  198,  300,  311,  347 

Deniker,  22 

De  Rechter,  186 

De  Rouville,  98 

De  Santi,  310 

De  Sinety,  406 

D'Espine,  M.,  55 

De  Vries,  118,  134 

Dickinson,  199 

Diesterweg,  147,  291 

Dieterich,  387 

Dieulafoy,  94 

Dobson,  97,  305 

Doflein,  248 

Doleris,  163,  296 

Donati,  150,  309 

Donitz,  466 

D'Or,  168 

Doran,  161,  162,  296,  363 

Doubleday,  353 

Doultrelepont,  187,  194 

Dovey,  371 

Doyen,  189,  231,  236 

Drake,  37 

Drebbel,  130 

Dreykorn,  162 

Driesch,  139,  222 

Dubar,  167 

Dubois,  186 

Du  Castel,  490 

Du  Chaillu,  14 

Duchatelet.  277 

Duges,  223,  225 

Duhamcl,  116 

Duhring,  484 

Duncan,  M.,  196,  275 

Dungern,  94 

Duplay,  179,  186 

Dupuytren,  183,  194 

Durante,  143,  144,  251 

Otirch,  463 

Durham,  167 

Dutrochet,  121,  122 

Duzan,  325 

KABLE,  361 
Eastwood,  463 
Eberlin,  161,  162 
Ebermann,  419 


INDEX  OF  NAMES  OF  AUTHORS  CITED 


511 


Ebinger,  105 

Ebse,  199 

Eckhardt,  329 

Eggel,  310 

Eggel  ing,  107 

Khroarcich,  111 

Ehrhardt,  329,  416.  427,  441 

Ehrlich,  189,  191,  471 

Eitihorn.  260 

Eiselsberg,  109,  192 

Eiselt,  419 

Eisendrath,  256 

Ekblom,  51 

Ellis,  A.  G.,  148 

Emanuol,  158,  304,  309 

Emmet,  145,  146,  151,  163,  275,  277 

Enderlin,  172,  175 

Engel,  42 

Engestrom,  363 

Englisch,  151,  282 

English,  T.  C.,  46 

Erbre,  187 

Erichsen,  288 

Esmarch,  341,  485 

Esmouet,  110 

Estlander,  448,  449 

Eve,  106,  111,  166,  248 

Evett,  147,  152,  155,  292 

Exnor,  254 

FABRE,  195,  263 

Fabre-Domerguo,  404 

Fagge  H.,  473 

Faidherbc,  425 

Fairbank,  H.  A.  T.,  387 

Falk,  161 

Faris,  97 

Farmer,  J.  B.,  217,  218,  219 

Fair,  W.,  27,  51,  60 

Fede,  97,  180 

Fehling,  153,  293 

Feinberg,  231,  245 

Feinstein,  362 

Fenwick,  S.,  279,  475 

Fere,  140,  170 

Fcrgusson,  462 

Fouchtwangor,  149,  293 

Fiaschi,  44 

Field,  Eva,  99 

Ficssingor,  263 

Findley,  330 

Fink,  420,  429 

Firket,  186 

Fischel,  147,  159,  160,  186,  277 

Fischer,  199,  307 

Fischer,  B.,  172,  227 

Fischer-Defoy,  441 

Fishberg,  M.,  18 

Fisher,  J.  H.,  461,  467 

Flaischlen,  158,  463 

Flatau,  163,  165,  293 

Fleischmann,  292 

Fletcher,  309 

Floury,  344,  495 

Flexner,  193 

Foa,  218,  237 

Foisy,  161 

Folliu,  182 


Forbes,  166 

Forbes,  G.,  338 

Ford,  J.  W.,  352 

Fordo,  44 

Fothergill,  232 

Foulorton,  103,  255,  257,  288 

Foulkos,  32 

Fournier,  284 

Fox,  W.,  339 

Fraenkel,  E.,  441,  460 

Fraisse,  224 

Francko,  231,  234 

Francotte,  186 

Frangenheim,  300,  306,  307,  308 

Frankel,  301,  305 

Franque,  304,  309,  339 

Freeman,  489 

Freire,  231,  234 

French,  152 

Frerichs,  334,  339 

Freund,  149,  153,  293.  408,  473 

Friedlander,  5,  173,  339 

Friedreich,  442,  446 

Frisco,  251 

Fritsch,  158 

Frontier,  94,  95 

Frothingham,  103 

Fuchs,  301,  362,  419,  439,  455 

Fiirst,  160 

Fiirstenberg,  102 

Fiitterer,  173,  199 

Fuzinami,  437 

GALABIN,  160 

Galen,  2,  10,  129 

Galeotti,  172,  218,  248,  404 

Galton,  F.,  362,  363,  374 

Ganghofncr,  329 

Garrigues,  164 

Garten,  174,  175 

Gaudier,  477 

Gaylord,  105,  184,  188,  189,  231,  244,  246, 

247,  363 
Gobele,  347 

Gebhard,  C.,  148,  158,  296 
Gebhardt,  113 
Geddes,  P.,  26 
Geets,  189,  236 
Goirsvold,  29 
Gcissler,  155,  180,  239 
Gellhorn,  158 
Gerdy,  168 
Germain,  151 
Gervais,  114 
Geyer,  295 
Geyl,  152 

Gibbes,  95,  237,  415 
Gibson,  161,  305,  359 
Giffen,  R.,  23,  65 
Gilbert.  172,  287 
Gilchrist,  174,  181,  255,  2(12 
Gilruth,  114 
Girode,  424 
Glatter,  277,  328 
Glauckler,  424,  425 
Glockner,  421 
Godin,  327 
Gootsch,  436,  437 


INDEX  OF  NAMES  OF  AUTHORS  CITED 


C.il.liiiium.  405,  407,  444,  445 

Qoldeohmidt,  J.,  43 

Gombault,  474 

Goodhart.  92,  335 

Goodman,  H.,  46 

Gordon,  340 

Gotte,  224 

Gottechalk,  151,  163 

Gouion,  182,  185.  193 

Gould,  492 

Gouley,  458 

Gow,  161 

Go  wen,  40 

Cowers,  R.  W.,  348,  385,  437 

Cowing.  96 

Graefe.  362 

Graham,  166 

Gratia,  96,  98,  187 

Graverry,  161 

Graviller,  305 

Grawitz,  271 

Gray,  32 

Greenough,  219,  247 

Griesinger,  43 

Griffiths,  287,  477 

Griffiths,  J.,  168 

Grimshaw,  70 

Grohe,  168 

Gross,  S.  W.,  167,  194,  274,  283,  294,  298, 
299,  326,  329,  383,  387,  416,  418,  419, 
420,  421,  422,  429,  431,  438,  449,  451, 
454,  456,  458,  488 

Gross,  D.  S.,  359 

Griiber,  205 

Griiner,  162 

Guarnieri,  248 

Guelliot,  195,  197,  263,  264 

Guende,  305 

Guermonprez,  195 

Guinard,  460 

Gulland,  334 

Gunsett,  161,  162 

Gurlt,  168,  279,  281,  282,  292,  295,  330,  387 

Gussenbauer,  413,  414,  435 

(iussorow,  150,  322,  328,  329 
Guthmann,  360,  304 
Guthrie,  216 
Guyot,  162,  168 

HAALAND,  188,  191 

Haberen,  287 

Haberer,  461 

Habermass,  487 

Habershon,  279 

Hacho,  457 

Hacker,  167 

Haeckel,  168 

Haeckcl,  E.,  135,  136,  137 

Hafbauer,  304 

Halm,  197 

Hahnsseau,  153 

Haig,  335 

Hake,  237 

Halipre,  364 

Halstead,  455 

Hamburger,  104,  105,  199 

Hamilton,  473 

Hanau,  109,  192 


Handford,  306 

Handley,  S.,  411,  446 

Hanot,  304 

Hansel,  429 

Hansemann,  184,  217,  218,  219,  244,  307, 

404,  405 
Hansen,  40 
Hardy,  347 
Harris,  S.,  15 

Harrison,  A.  J.,  94,  102,  110,  111 
Hart,  E.,  43 
Hartmann,  357 
Hartung,  473 
Harvey,  129 
:  Hasse,  164,  486 
Hathaway,  111 
Hauber,  292 
•   Haultain,  146 

Hauser,  147,  152.  235,  298,  307,  402 
!   Haussmann,  153  , 

Haviland,  30,  60,  79,  81,  83,  84,  264 
Haward,  429 
Hawes,  46 

Hayem,  235,  470,  471 
Hayward,  306 
Hearsey,  45 
Heckford,  329 
Heidenhain,  410,  466 
Heinbaum,  466 
Heinricius,  161,  164 
Heinsius,  153 
Heitler,  337 
Heitzmann,  206 
Hektoen,  174,  181,  256,  262 
Helmholz,  175 
Hemmeter,  173,  183,  219 
Henderson,  44,  306 
Henderson,  E.,  32 
Hendry,  489 
Henle,  149 
Henry,  329,  429 
Henoch,  422 
Herff,  153 
Herman,  G.  E.,  465 

Hermann,  168 

Hertaux,  285, 

Licrtwig,  139,  209 

Herzog,  184,  193 

Heurtaux,  167/305,  308,  460 

Heusinger,  111 

Hewlett,  R.  T.,  248,  409 

Hicks,  B.,  165 

Hildaus,  F.,  152 

Hildcbrand,  414 

Hilgendorf,  110 

Hillier,  W.  T.,  424,  425,  432 

Hilt,  477 

Hinds,  307 
;   Hippocrates,  22,  50,  357 

Hirschberg,  301 

Hirschmanu,  158 

Hirst,  147 

Hirtz,  328 

Hobbs,  345 

Hobday,  97,  99,  102 

Hodge,  165 

Hodgkinson,  J.  F.,  106 
!   Hofer,  151 


INDEX  OP  NAMES  OF  AUTHORS  CITED 


513 


Hoffmann,  F.  L.,  18,  56 

Hofmeier,  158,  303,  325,  411,  455 

Hofmeister,  117 

Hoggan,  410 

Hollander,  153,  361,  362 

Honda,  247 

Howe,  164,  329 

Howitz,  162 

Howse,  335 

Huber,  164 

Hudson,  L.,  97 

Hue,  347,  364 

Hueter,  167,  328 

Hufeland,  496 

Hugonberger,  150 

Hugnenin,  428 

Hulke,  163,  171,  427,  461 

Humphry,  320 

Hunner,  293 

Hunter,  J.,  3,  88,  100, 131, 171,  176,  233,  489 

Hunter,  W.,  31 

Hurlemont,  425 

Hutchinson,  J.,   100,   103,   112,  270,  283, 

303,  304,  305,  352,  426,  458 
Hutchinson,  Woods,  91,  93,  94,  101, 112,  360 
Hutchison,  R.,  442 
Huxley,  208 
Hyatt,  194 
Hyde,  174,  181,  256,  262 

IDE,  206,  405 
Isch-Wall,  835,  474 
Israel,  183,  243,  262 
Iterson,  359 

JACKSON,  162,  164,  328 

Jackson,  H.,  356 

Jacobs,  189,  236 

Jacobson,  148 

Jahr,  343,  494 

Jakob,  471 

Jaksch,  475 

Jalland,  330 

Janeway,  474,  486 

Janssen,  130 

Janvrin,  164 

Jeaffreson,  K.,  20 

Jeannel,  187 

Jenks,  162 

Jensen,  91,  108,  187.  188,  189,  190,  191 

Jessett,  B.,  485 

Jobling,  193 

Jobson,  104 

Jolmo,  89,  90,  91,  95,  100  . 

Johnson,  O.,  44 

Johnston,  152,  155 

Johnston,  G.  B.,  161,  162 

Jones,  E.  L.,  267 

Josephson,  162,  164 

Journadet,  47 

Juergens,  184,  185,  194,  231,  243 

Juler,  419 

Juliusberger,  51 

Jung,  97 

KAHANE,  252,  470 
Kallenberger,  339 
Kallins,  165 


Kaitenbach,  462 

Kanthack,  237 

Kaposi,  308,  484 

Kappeler,  259,  334 

Karewski,  303 

Kaschewarowna-lludnewa,  93 

Kaufmann,  158,  170,  200,  303,  309,  433,  434 

Kaul,  150,  153 

Kautorowicz,  430,  448 

Keen,  248 

Kehr,  281,  336 

Keiffer,  97,  162 

Keith,  364 

Keller,  304,  309 

Kellet-Smith,  45 

Kelly,  364 

Kelynack,  338 

Kerr,  31 

Kesteven,  306 

King,  W.  A.,  18 

Kirmisson,  43,  425 

Kiwisch,  452 

Klebs,  186,  199,  218,  237,  303,  404,  413 

Klein,  150,  255   / 

Kleinwachter,  145 

Klippel,  474,  475 

Klob,  291 

Klotz,  159,  299,  448 

Knaggs,  306 

Knapp,  446 

Knauer,  175 

Knox,  148,  164 

Kober,  300 

Kobner,  484 

Kocher,  460 

Kohlbriigge,  42 

Kolb,  29,  494 

Kompe,  361 

Kopfstein,  239 

Korstneff,  231,  240 

Korte,  107 

Korteweg,  359,  361 

Koster,  187,  328 

Kratzenstein,  464 

Krause,  407 

Krawkow,  477 

Kretz,  307 

Kreutzmann,  259,  334 

Krishaber,  94 

Kronig,  304 

Krukenberg,  457 

Kiibasoff,  231,  234,  235 

Kuhn,  194,  328 

Kulmart,  155,  309 

Kullmann,  470 

Kummer,  309 

Kurloff,  240 

Kurpjuweit,  436,  472,  473 

Kursteiner,  168 

Kussmaul,  160 

Kiister,  151,  299,  414,  420 

Kuthy,  371 

Kuttner,  328 

Kworostansky,  293 

LABBE,  166,  294 
Lack,  L.,  108,  172 
Ladinski,  300 

33 


514 


INDEX  OF  NAMES  OF  AUTHORS  CITED 


Lurmire,  130 

Lafforo,  148 

Uidlcy,  329 

Lakor,  470 

Lamarck,  136 

Lambo,  W.,  352 

Lambotte,  342,  343 

Lampiazi-Rubino,  231,  234 

Lancereux,  186,  483 

Landau,  144.  150,  291,  309 

Landois,  224 

Landouzy,  328 

Landry,  47 

Lang,  483 

Lange,  167,  451 

Langenbeck,  182,  183 

Langhans,  413 

Langlois,  96 

Langton,  303 

Lanz,  O.,  177,  180,  185 

Lapointe,  308,  486 

Lardennois,  432,  445 

Laspeyres,  29,  314 

Latteux,  260 

Lawford,  301,  361,  363,  439,  441,  456 

Lawrie,  200,  363 

Lazarus-Barlow,  20,  283,  327,  416,  431,  438 

Leaf,  367,  411,  444 

Loale,  177 

Leared,  363 

Lebard,  234 

Lebert,  96,  100,  149,  151,  219,  231,  277, 

289,  299,  306,  311,  316,  361,  407,  435, 

454,  475 

Leblanc,  91,  92,  103 
Lecene,  110,  167,  168,  308 
Le  Count,  218,  244 
Lediard,  98,  101 
Leeuwenhoek,  129 
Lefas,  97 
Le  Gemtel,  300 
Le  Goupils,  338 
Legrain,  43,  347 
Legros,  176 
Legueu,  291 
Leichtenstein,  367 
Leiden,  99 
Leisering,  97 
Leitch,  349,  417,  433 
Leloir,  167 
Leo,  163 
Leon,  98 
Leopold,  153,  174,  175,  177,  199,  200,  231, 

253,  262,  413,  457,  460,  466 
Leplay,  186,  260 
Leser,  167 
Letienne,  432 
Leube,  422 
Leuckhart,  248 
Levin,  170,  172,  175 
lowers,  161 
Lowin,  477 
Leyden,  231,  242 
Lidner,  328 
Liebig,  136 
Liebmann,  291 
Lienaux,  96,  98 
Limacher,  427 


Limbeck,  471 

Linser,  216 

Lister,  130 

Livingstone,  45 

Ljunggren,  169 

Lockver,  161,  162,  311 

Loeb;  L.,  104,  109,  110,  170,  173,  174,  180, 

188,  191,  192,  193,  209,  210,  225,  309, 

404,  413,  445 
Loffler,  340 
Lohlein,  168,  364 
Lomer,  496 
Looten,  301 

Louis,  P.  C.  A.,  130,  340,  474 
Lowitt,  184,  471 
Lubareoh,  108,  170,  175,  247,  310,  338,  339, 

344,  475 

Liicke,  139,  166,  199,  433 
Luminezen,  304 
Lunn,  151,  330,  335 
Lunn,  J.  R.,  346 
Luschi,  496 
Lusk,  169 
Lustig,  218 
Luton,  279 
Lwofi,  175 
Lyford,  329 
Lyle,  161 
Lynds,  162 
Lyon,  19 

MAAS,  175 

MacCasky,  338 

MacDonald,  G.,  41,  78 

MacEwen,  195 

MacFadyean,  89,  95,  96,  98,  99,  100,  101, 

102,  103,  105 
MacGregor,  W.,  42 
MacKay,  492 
Mackenrodt,  466 
Mackenzie,  162,  164 
Mackenzie,  M.,  97 
Mackenzie,  S.,  484 
Madden,  F.  C.,  35,  43 
Maeder,  74 
Maffuci,  251 
Maggi,  225 
Magitot,  176 
Mahomed,  151 
Maier,  155,  308,  309,  310 
Malassez,  237 
Malone,  288 
Malpighi,  129 
Malvey,  257 
Manders,  H.,  258 
Mandry,  299,  301 
Mangiagalli,  162 
Manichon,  361 
Maniscalio,  173 
Mann,  248 
Mannel,  151 
Maragliano,  236 
Marchand,  98,  151 
Marks,  301 
Marnoch,  171 
Marsh,  H.,  488 
Marshall,  151 
Marten,  169 


INDEX  OF  NAMES  OF  AUTHORS  CITED 


515 


Martin,  161,  162,  277,  293,  452,  462,  473 

Martinotti,  156,  403 

Marx,  181 

Mason,  H.,  267 

Masse,  170,  172 

Massen,  302 

Masterman,  490 

Masters,  117,  118 

Matas,  15 

Mathis,  193 

Matthews,  210 

Mauclaire,  163 

Maudsley,  372 

Maupas,  205,  206 

Mayet,  181,  186 

Mayor,  168 

Maxwell,  J.  P.,  31 

McCarthy,  103 

McCone,  175 

McLeod,  38 

Mead,  209 

Meadows,  145 

Mears,  151,  163 

Megaw,  38 

Mendel,  374 

Menetrier,  424,  425 

Mercanton,  303,  304 

Meredith,  462 

Merkel,  148 

Merkens,  489 

Merriman,  151 

Metchnikoff,  93,  232,  237,  240,  272 

Meurer,  161 

Meyer,  409,  477 

Meyer,  R.,  147,  148,  149,  150,  151,  153 

Michael,  302 

Michaelis,  111 

Michaux,  327 

Michelsohn,  299,  305,  306 

Miles,  384 

Milford,  304,  309 

Milian,  310 

Mill,  J.  S.,  353 

Miller,  149 

Milne,  327 

Minot,  203 

Moak,  338,  339 

Model,  168 

Mohr,  H.,  496 

Molliere,  327 

Monod,  28,  103,  448 

Monsarrat,  98,  231,  252,  253 

Montgomery,  304,  309 

Moore,  B.,  173,  473 

Moore,  C.  H.,  30,  79,  81,  82,  360,  372 

Moore,  J.  E.  S.,  189,  217,  218,  219 

Moore,  N.,  328,  417,  434,  435,  436,  437 

Moquin-Tandon,  124 

Moraczewski,  Sophie,  473 

Morau,  188,  189,  190 

Morgagni,  167 

Morgan,  T.  H.,  139,  209 

Morestin,  305,  464 

Morison,  R.,  464 

Morris,  45 

Morris,  H.,  283,  284,  285,  429 

Mosher,  281,  336 

Morton,  C.  A.,  167,  171,  306 


I   Moty,  236 
j  Mougie,  111 

Moynihan,  486 

Moxon,  157,  199,  230,  414 

Mueller,  224 

Muir,  336 

Muirhead,  C.,  51,  56 

Mulhall,  64,  65,  68,  71,  73 

Miiller,  F.,  476,  477 

Miiller,  J.,  8,   10,  96,  131,  156,  157,   167, 
168,  219,  231,  270,  271,  403,  407 

Muller,  P.,  462 

Mullins,  77,  78 

Munde,  161,  329 

Murchison,  311,  336 

Murray,  113 

Mygge,  357 

NADIG,  432 

Naegeli,  338,  339 

Nagel,  150 

Nash,  W.  G.,  267 

Nason,  E.  N.,  265 

Nehrkorn,  305,  307 

Neill,  164 

Nelaton,  167 

Nencki,  24,  70 

Nepveu,  233,  442 

Neugebauer,  153,  164,  167,  465 

Neumann,  162 

Neureutter,  328 
:  Neve,  E.  F.,  35 
:  Newman,  51 

i  Newsholme,  A.,  52,  55,  56,  58,  351 
!  Newton,  I.,  130 
i   Newton,  R.  E.,  362 

Niblock,  38 

Nicholls,  298,  300,  305,  338 

Nichols,  E.  H.,   140,   159,   170,   172,   175, 

176,  257 
!  Nicolle,  364 

Niebergall,  199,  304,  309 

Niessen,  231,  261,  470 

Nieuwenhuis,  42 

Nightingale,  40 

Noble,  C.  P.,  196,  291 

Nocard,  107 

Noel,  194,  265 

Nosske,  247 

Notthaft,  306 

Novinsky,  193 

Nunn,   T.,  299,   316,   319,   335,   367,   449, 
450,  459,  460 

Nussbaum,  205 

OBICI,  262 
Odebrecht,  452 
Ogle,  W.,  318 
Ohlmacher,  113,  114 
O'Kinealy,  177 
Old,  45 
Oldekop,  429 
Olivier,  167 
Oilier,  166,  169 
Olshausen,  462 
Olt,  244 
Orloff,  147 
Orth,  148,  306 

33—2 


516 


INDEX  OF  NAMES  OF  AUTHORS  CITED 


Orthmann.  151,  164 

Ortschild,  95,  96,  97 

Otto  88,  93,  110,  111,  112,  113,  114,  362 

Osier,  W.,  328,  364,  491 

Owen,  I.,  351 

Owen,  R.,  136,  140,  207,  208 

Owens,  174,  181,  256,  262 

PACINOTTI,  407 

Pagel,  42 

Pa|et,  J.,  5,  106,  143,  144,  282,  294,  319, 

335,  336,  349,  360,  426,  494 
Paget,  S.,  120 
Pamard,  460 
Panas,  305,  486 
Pamim,  20 
Paquet,  432 
Park,  Mungo,  350 
Parker,  111 
Parona,  148 

Parsons,  H.,  307,  432,  435,  439,  4-11 
Pasteur,  232,  259 
Patel,  429 

Paterson,  P.,  217,  218 
Patterson,  111 
Patteson,  100 
Pauchet,  161 
Paul,  301 
Paulicki,  110 
Payne,  J.  F.,  54,  177,  339 
Peacock,  363 
Pean,  163,  360,  460 
Pearson,  K.,  315,  357,  367 
Pease,  184 
Peiser,  420 
Pelletan,  148 
Pemberton,  O.,  143,  419 
Penberthy,  90,  101,  180 
Penrose,   164 
Pernice,  148 
Perrion,  343,  494 
Perry,  A.,  39 
Perry,  E.  C.,  280,  436 
Petersen,  254,  298 
Petit,  425 

Petit,  G.,  95,  96,  97,  98,  99,  100,  101,  102 
Petrick,  415 
Petry,  219,  408 
Pfannenstiel,  199,  296,  464 
Pfeiffer,  185,  231,  237,  238,  245,  246,  248 
Piana,  225 

Pianese,  237,  241,  405 
Pichot,  276,  322,  452 
Pick,  9,  97,  111,  112,  114,  181,  300 
Pick,  L.,  144,  150,  161,  162,  463 
Pi  cot,  325 
Pied,  167 

Pierallini,  172,  248,  404 
Piering,  158 
Pike,  100,  104 
Pilliet,  167 
Pinatelli,  436 
Pinel,  475 
Pirogoff,  288 
Pitts,  B.,  437 
Playfair,  465 
Plehn,  Fraulein,  44,  113 
Plicque,  458 


Plimmer,  231,  240,  241 

Podwyssotski,  246,  405 

Poinsot,  326 

Polaillon,  171 

Poll,  91,  97,  111,  112 

Pollard,  B.,  287 

Pollock,  103 

Pollosson,  164 

Poncet,  262,  425 

Porak,  442 

Porter,  163 

Poulsen,  305,  416,  420,  422,  458 

Poupinel,  464 

Power,  D'Arcy,    166,   172,    186,  239,  248, 

263,  264 

Power,  J.  H.,  359 
Pozzi,  151,  462 
Prinzing,  29 
Puzey,  287 

QUKNU,  407 
Quesnel,  73 
Quinquaud,  470 

RABENAU,  146 

Rabinowitsch,  Lydia,  94,  109 

Rabl-Ruckhardt,"  304,  309 

Raff,  347 

Ranvier,  406,  416 

Rappin,  231,  234 

Rappok,  273 

Rasch,  40 

Rayer,  91 

Raymond,  425 

Raw,  N.,  425 

Ready,  256 

Recaraier,  143 

Recklinghausen,  147,  150,  152,  153,  291, 
416,  428,  446 

Reclus,  364 

Registrar-General  of  England  and  Wales, 
27,  28,  51,  52,  55,  57,  58,  60,  66,  77,  81, 
82,  83,  295,  312,  313,  315,  316,  317,  318, 
319,  320,  321,  323,  324,  329,  354,  381 

Registrar-General  of  Ireland,  28,   69,   70, 

372 

1  Registrar-General  of  Scotland,  28,  67,  68,  69 
;  Reiche,  281.  282 
i  Reichel,  304 

Reid,  155 

Reifsnyder,  Elizabeth,  31 
i  Reinecke,  200 

Remak,  131,  143 

Rendu,  151 
;  Renner,  418 

Renon,  262 
I  Renshaw,  110 
;  Reverdin,  168,  169 

Ribbert,  137,  147,  151,  152,  168,  170,  171, 
172,  175,  237,  377,  406 

Richardson,  495 

Richardson,  B.  W.,  16 

Richardson,  O.,  247 

Richet,  235,  294 

Richmond,  C.  E.,  488 

Richter,  304,  306,  307 

Ricker,  147,  150,  153,  291 

Ricketts,  256,  260,  262 


INDEX  OF  NAMES  OF  AUTHORS  CITED 


517 


Ricochon,  372 

Bicord,  341 

Bidewood,  102 

Ridler,  99,  102 

Rieder,  150 

Rieffel,  456,  458 

Riehl,  475 

Ries,  158 

Riga.  97,  180 

RindHeisch,  167,  407 

Risel,  436 

Ritchie,  151 

Roberts,  L.,  483 

Robertson,  231,  246 

Robson,  M..  279,  280.  281,  306,  486 

Rocher,  168 

Rodman,  15,  47,  282 

Roehrig,  291 

Roger,  89,  95,  96,  99,  101,  105,  172,  287 

Rogers,  300 

Rokitansky,  151,  155,  219,  220,  494,  495 

Rolleston,  96,  98,  281,  301,  336 

Roily,  291 

Roraiti,  162 

Rommelacre,  476 

Roncali,  250 

Roper,  362 

Rosenbach,  306 

Rosenstein,  152,  309,  329 

Roser,  143 

Rosger,  145 

Rossa,  164 

Roth,  40,  78 

Roth  well,  260,  262 

Rouget,  189 

Rousseau,  424,  425 

Rousseau,  E.,  91,  110,  112 

Routh,  162 

Routier,  167 

Roux,  163 

Roux,  W.,  139,  140,  222 

Ruffer,  231,  237,  238,  240,  247 

Ruge,  276 

Russell,  199,  304 

Russell,  W.,  231,  249 

Rutherford,  306 

SABATIER,  466 

Sajous,  215 

Salkowski,  408 

Salter,  176 

Sanarelli,  231,  234 

Sandheimer,  164 

Sandifort,  113 

Sanfelice,    110,    174,    179,    190,   231,    240, 

249,  250,  251,  252,  262,  427,  485 
Sanger,  151,  152,  465,  475,  494 
Saundby,  103,  280 
Sato,  461 
Savariaud,  166 
Savor,  465 
Sawtchenko,  247 
Saxer,  262 
Scanzoni,  494 
Schael,  305 
Schamberg,  260 
Schaper,  290,  445 
Schaudinn,  231,  233,  242 


Schauta,  158.  303,  328,  420,  465 

Scheffer,  328 

Schenk,  436,  465 

Scheren,  301 

Scheuerlen,  231,  234 

Schill,  231,  234 

Schiller,  306,  433 

Schimmelbusch,  200,  302 

Schlagenhaufer,  436 

Schleiden,  117,  131 

Schlesinger,  280 

Schmidt,  164,  278 

Schmidt,  B.,  168,  420,  427,  460 

Schmidt,  J.(  162 

Schmidt,  M.  B.,  444,  445,  446 

Schmidt,  O.,  190,  231,  245 

Schmieden,  310 

Schmincke,  304 

Schmorl,  309,  328,  443 

Schneyer,  473 

Schoening,  327 

Schopf,  200 

Schramm,  425 

Schroeder,  277,  407 

Schubert,  300 

Schuchardt,  158 

Schiiller,  M.,  231,  243 

Schultze,  O.,  165 

Schuoler,  438,  454 

Schutz,  91,  176,  235 

Schwalbe,  339 

Schwann,  131 

Schweizer,  97 

Schweniger,  170 

Schwimmer,  284 

Scott,  45,  114,  265 

Scott,  W.  M.,  101 

Scudder,  442 

Seeger,  148 

Seelig,  410,  411,  413 

Seligmann,  176,  180 

Selligues,  130 
i  Semb,  296 
•  Semmer,  94 

Semon,  296 

Senger,  186,  234 

Senn,  N.,  150,  186,  196,  198,  287 

Sequeira,  216 

Settegart,  461 

Seydel,  148,  149 

Sharp,  106 

Shattock,  93,  108,  110,  172,  176,  183,  186, 
194,  217,  234,  238,  240,  287 

Shaw,  198 

Shaw,  B.,  339 

Shaw,  L.  E.,  280,  436 
i  Shaw-Mackenzie,  216 

Shield,  M.,  283,  285,  488 

Shoemaker,  152 
i  Shottlander,  147 

Sibley.  J.  W.,  96,  316,  359,  364,  459 
,  Sibley,  W.  K.,  113 

Sichel,  362 

Siebold,  363 

Sieveking,  A.  B.,  45 

Sigg,  494 

Silcock,  98,  248,  361.  363,  364 

Silex,  339 


518 


INDEX  OF  NAMES  OF  AUTHORS  CITED 


Simon,  469 

Simpson,  364 

Simpson,  J.  J.,  346 

Simpson,  J.  Y.(  226,  275,  329 

Sinclair,  W.  J.,  65,  66 

Singer,  C.,  44 

Sirleo,  251 

Sjobring,  N.,  231,  242,  243 

Skchiwan,  257,  258 

Skene,  153 

Slater,  112 

Smallwoods,  113 

Smith,  B.,  180,  187 

Smith,  G.,  486 

Smith,  M.,  495 

Smith,  R.  W.,  102 

Smith,  T.,  148.  189,  364 

Smith,  W.  M.,  153 

Smyly,  311 

Snegurieff,  161 

Snell,  S.,  362,  486 

Snow,  H.,  345,  486,  495 

Sobotta,  145 

Sodre,  49 

Sorel,  263 

Soudakewitch,  231,  237,  238,  240,  247 

Spallanzani,  224 

Spemann,  226 

Spencer,  Herbert,   1,   118,   135,  '136,   137, 

202,  203,  206,  213,  220 
Spencer,  H.  R.t  155,  308,  465 
Spencer,  W.  G.,  98,  99,  103,  109 
Spinelli,  329,  425 
Spirlas,  248 
Spitzley,  486 
Spitzly,  48 
Sprengel,  362,  429 
Spreull,  105 
Stefanini,  167 
Steiner,  328 
Steinhauser,  283,  302 
Stevens,  W.  M.,  425 
Stewart,   152 
Sticker,  89,  90,  91,  92,  94,  99,  101,  104, 

105,  106,  107,  179,  180,  181,  215 
Stilling,  167 
Stockard,  163 
Stokes,  174,  255 
Stone,  146 
Strode,  99 

Strcebe,  218,  237,  405 
Stroinski,  148 
Striimpell,  362 
Suchardt,  301 
Sumpter,  301 
Sutherland,  D.  W.,  34 
Swan,  295 
Switalski,  151 
Sy miners,  347 
Symons,  W.  H.,  268,  269 
Szumann,  307 

TAIT,  L.,  114 

Tanner,  277 

Tate,  311 

Tatham,  J.  F.  W.,  28,  55,  58,  315,  354 

Taylor,  155 

Taylor,  B.,  97,  100 


Teacher,  306,  324,  418 
Teallier,  343,  495 
Teissin,  364 
Terrier,  311 
Terrillon,  148,  299,  448 
Terry,  43 
Therese,  158 
Thierfelder,  307 
Thiersch,  10,  169,  407 
Thoma,  231,  237,  413 
Thomas,  162 
Thompson,  C.,  302 
Thompson,  R.,  371,  372 
Thompson,  R.  L.,  429 
Thomson,  A.,  102 
Thorn,  199,  292 
Thorne,  164 
Thornton,  163 
Tillmanns,  302 
Tiriant,  43 
Topfer,  476 

Torok,  412,  421,  431,  432 
Tourneux,  147,  150 
Townsend,  M.,  23 
Tracy,  260 
Trasbot,  99 
Trecul,  122 
Trembley,  222,  223 
Treub,  151 
Treves,  F.,  109,  148 
Tripier,  193 
Troisier,  422,  425 
Tross,  197 

Trotter,  88,  104,  105 
Tschop,  329 
Tuboef,  246 
Turner,  259,  334 
Tully,  130 
Tulpius,  N.,  195 
Turenne,  342 
Twort,  188 
Tyzzer,  109 

ULESKO-STROGANOWA,  292,  293 
Ullman,  163 
Unger,  425 
Unna,  347 
Urquhart,  345 

VALENCIENNES,  114 

Van  Beneden,  211 

Van  der  Burg,  42 

Van  der  Byl,  168 

Van  der  Kolk,  407 

Variot,  177 

Vedel,  184 

Veit,  151,  276,  296,  360,  443 

Velich,  109,  192 

Velitz,  463 

Velpeau,    168,    282,    299,    359,    383,    430, 

448,  449,  459 
Vennemann,  199 
Verneuil,  143,  153,  235,  335,  407,  424,  448. 

460,  482 
Viannay,  425 
Viborg,  97 
Vicq  d'Azyr,  152 
Vidal,  425 


INDEX  OF  NAMES  OF  AUTHORS  CITED 


519 


Vierregge,  329 

Villiers,  158 

Villy,  F.,  476 

Vineburg,  164 

Virchow,  3,  11,  55,  96,  97,  98,  100,  102,  104, 
105,  131,  132,  141,  143,  144,  164,  183, 
204,  231,  237,  270,  287,  308,  310,  325, 
344,  363,  422,  429,  438,  471 

Vogel.  183,  185 

Volcker,  244 

Volkmann,  273,  299,  302,  448,  460 

Vulpian,  225 

WADE,  H.,  231,  246 

Waghorn,  105 

Wagner,  97,  155,  161,  167,  436 

Wakefield,  151,  421 

Waldenburg,  116 

Waldeyer,  10,  173,  294,  404,  413 

Waldmann,  101 

Walker,  C.  E.,  189,  217,  218,  219 

Walker,  G.,  301 

Walker,  J.  H.,  231 

Walker,  J.  W.  T.,  416,  433 

Wallace,  96 

Wallert,  339 

Walshe,  W.  H.,  30,  277,  304,  407,  494 

Walter,  199,  301,  304,  307,  310 

Walther,  143,  432 

Warder,  164 

Waring,  8,  156,  157,  231,  403,  409,  414 

Warren,  J.  C.,  167,  283 

Warren,  J.  M.,  361,  362,  364 

Warthin,  301.  339,  444,  486 

Washbourn,  180,  187 

Watts,  151 

Webb,  J.  H.,  85,  352 

Webb,  T.  L.,  263 

Webber,  100 

Weber,  F.  P.,  338,  364 

Wehr,  91,  179,  180,  187 

Weigert,  137,  181,  186 

Weil,  101 

Weinberg,  254 

Weismann,  A.,  117,  135,  136,  210,  211,  213, 

223,  357 

Welch,  279,  280,  328 
Woldon,  225 
Wells,  309,  310 
Wells,  S.,  148,  464,  465 
Welsh,  110,  484 
Weltner,  111 
Wendelstadt,  224 
Wentscher,  169 
Wertheim,  164,  421 
West,  275,  278 
Wetherill,  163 
Whipham,  T.  R.  C.,  426 
White,  180 


Wickham,  186,  196,  231,  237,  238 

Wiggin,  151 

Wigglesworth,  345 

Wild,  283 

Wilder,  363 

Williams,  A.,  198 

Williams,  A.  J.,  97 

Williams,  E.  H.,  97 

Williams,  H.  V.,  98 

Williams,  J.,  277,  303,  322,  453 

Williams,  J.  W.,  91 

Williams,  Whitridge,  152,  155,  293 

Williamson,  328 

Wilms,  168 

Wilson,  E.  B.,  138,  139,  140,  213,  222 

Wilson,  H.,  362 

Wilson,  T.,  421 

Winckel,  163,  274,  277,  311 

Windle,  105,  363 

Winiwarter,  303,  305,  420,  429,  456 

Winter,  158,  199,  303,  411,  420 

Winternitz,  462 

Wintersteiner,  301 

Witte,  148 

Wittelshofer,  412,  421,  431,  432 

Wlaeff,  110,  254 

Wolf,  K.,  339 

Wolff,  183,  224,  262,  288 

Wolff,  A.,  351 

Wolff,  C.  F.,  204,  205,  208 

Wolstenholme,  103 

Woolley,  300,  301 

Woskresensky,  151 

Wright,  A.  E.,  236 

Wright,  G.  A.,  328 

Wutzdorff,  74 

Wyss,  173,  183 

YOUNG,  288 
Young,  H.,  407 
Young,  L.,  47 
Young,  R.  A.,  304,  305 

ZACHAEIAS,  206 

Zacutus,  N.,  195 

Zade,  436 

Zahn,  174,  235,  338,  348,  422 

Zappert,  472 

Zehnder,  414 

Zeiss,  304 

Zeller,  158 

Zenker,  339 

Ziegler,  181,  229 

Zieman,  102 

Ziemssen,  346 

Zimmermann,  307 

Zink,  105 

Zoja,  222 

Zweifel,  164,  329 


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